•Development of hand knitted biocompatible composite meshes with dip coating.•Formation of SF mesh surface functionalized with polymer-natural extracts.•Meshes underwent physical characterizations, in vitro biological testing, in silico molecular docking, and in vivo analysis.•The composite meshes were non-cytotoxic, antimicrobial, and up-regulated gene expression.•PHBV-HE composite mesh facilitated soft tissue repair and regeneration. Post-operative complications stemming from incompatible meshes often lead to delayed wound healing, seroma, infections, inappropriate tissue infiltration and pain. The present study was outlined to develop biocompatible composite hand-knitted silk meshes modified with polymers and natural extracts. Our study introduced hand-knitted B. mori silk fibroin as the primary mesh material, offering superior mechanical strength and biocompatibility. The spin-assisted dip coating achieved desirable morphology, internal structures, thickness, and surface roughness. Moreover, the application of biopolymeric composite coatings containing polymers and natural extracts introduced antimicrobial character, facilitated cell attachment, migration, proliferation, potentiating gene expression and accelerating the process of wound healing. These composite meshes are a viable solution for addressing post-op complications in hernia and soft tissue repair surgeries. In this study, 9 silk-based composite meshes (modified with polymeric-extract blends through spin-assisted dip coating) were successfully developed. Experimental variants were then subjected to various characterizations including SEM, DMA and chemical analysis (FTIR and GC-MS). Modified meshes were evaluated for their physiological characteristics and biological responses (the basic criterion for the selection of composite silk mesh). The biological testing included (antimicrobial susceptibility testing, in vitro cell viability assay, cell attachment assay (NIH3T3 and hUc-MSCs), in vitro cell migration, in vitro gene expression analysis with NIH3T3, in silico molecular docking with bioactive ligands of HE extract and in vivo analysis with PHBV-HE and PHBV-Control composite meshes in rat models. Results showed that all variants exhibited a multi-fiber morphology with significant surface coating, allowing for optimal drug release up to 72 h. This release facilitated antibacterial properties and biocompatibility, as evidenced by in vitro cell viability, migration assays and gene expression analysis. Among the variants, the PHBV-HE composite mesh demonstrated superior results. In the case of PHBV-coated polymeric controls, the SEM analysis concluded that the presence of coating reduced the pore size up to 39.62 % whereas, fiber diameter was increased by up to 19.89 % as compared to the control. The presence of a coating on the mesh improved the mechanical strength/modulus by 165.89 %, UTS by 185.38 % and reduced the % strain by 64.67 %. The fast release of HE from PHBV-HE composite mesh was 90.7% up to 72h, confirming that it can induce antibacterial activity against surgical infections. PHBV-HE showed the highest cell viability, wound healing and gene expression. Based on appreciable biological evaluation results shown by PHBV-HE, in rat hernia models, only the PHBV-HE variant was tested for in-vivo analysis. Results confirmed its non-toxic nature and wound-healing abilities. Enhanced cell proliferation and wound healing observed both in vitro and in vivo indicated that PHBV-HE holds promise as a biomedical implant suggesting its potential for effective hernia and soft tissue repair and regeneration. The quest for an ideal mesh solution for potentiating soft tissue repair and regeneration is a long road with infinite horizons. Hence, the application of natural biomaterials, polymers and natural extracts with specialized textile techniques can emerge as a futuristic approach to fabricating a versatile mesh design and composition. The present study was conducted to develop novel and functional surface functionalized antimicrobial and biocompatible knitted silk fibroin meshes for soft tissue and hernia repair by incorporating the principles of tissue engineering. Different polymer composites along with honey bee products were utilized to enhance morphological, biomechanical, antimicrobial and biocompatible characteristics to support soft tissue and hernia repair. Display omitted