•This review unravels the regulation of plant secondary metabolites under biotic stress.•The mechanism of action of plants' secondary metabolites to innate immunity is also highlighted.•Insights into regulation of transcription factors under biotic stress are also elaborated. Secondary metabolites in plants have been recognized as a novel basis of potential bio-pesticides, paving the way for their use in sustainable agriculture. Plant secondary metabolites have pivotal roles in plant-pathogen interactions. Some important secondary metabolites of plants are terpenoids, flavanols, flavones, etc., are stress-inducible phytochemicals playing an important role in plant immune response development. Pathogen enters into host cell, multiply and utilise the biological mechanism of plants, causing a hazard to world food assembly. Under stressed circumstances, plants evolve a powerful and intricate system of growth and defensive action. On the other hand, transcription factors (TFs) assist host plants to counter adverse environments by acting as mediators of stress signal and regulating the stress-responsive gene expression. The transcriptional and post-transcriptional manipulation of transcriptional factors is capable of aid in molecular breeding and genetic modification meant for improved secondary metabolite synthesis. Although the presence of numerous secondary metabolites has been established in plant life, very slight is known about their interaction with pathogens and the specific mechanisms involved in leading to plant immunity. Chemical pesticides are wreaking havoc on our environment. As a consequence, environmental-friendly alternatives to disease management, like plant-based metabolites, should be explored. In this appraisal, we have reviewed plant secondary metabolites in relation to pathogens, their contribution to innate immunity, mechanism of action, and regulation of TFs in response to combating plant infections in an eco-friendly approach.