The main of the present study was to prepare chitosan (Chit) and chitosan hydroxyapatite nanoparticle (Chit-nHap) to assess their activities against two major diseases affecting tomato crop: pepino mosaic virus (PepMV) and verticillium wilt caused by the fungus Verticillium dahliae. The synthesized compounds were characterized using X-rays diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electronic microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). In vitro, the application of various concentrations of Chit and Chit-nHap showed significant inhibition of radial mycelial growth against V. dahliae. However, Chit-nHap was found to be more effective than Chit. In greenhouse trials, the disease severity was significantly reduced when Chit and Chit-nHap were sprayed to the leaves at 150 and 250 μg mL−1. The highest concentration of Chit and Chit-nHap reduced leaf alteration index by more than 81% and browning index by 96%. Both compounds also reduced PepMV disease severity and virus accumulation. Protection afforded against PepMV was associated with differential accumulation of H2O2 and with potentiation of the activity of antioxidant enzymes such as catalase, ascorbate peroxidase, guaiacol peroxidase and polyphenol oxidase. •Chitosan nanohydroxyapatite was synthetized and characterized.•Chitosan nanohydroxyapatite reduced Verticillium wilt and PepMV severity in tomato.•Protection against PepMV was associated with modulation of antioxidant defenses.