In recent years, the unprecedented increase in various cancers such as melanoma has caused researchers to focus more on the formulation of newer drugs with less side effects. In this study, we herein indicate the biogenic nanoarchitechtonics of Ag NPs template over chitosan/starch mixed hydrogel having notable reducing potential and anti-malignant melanoma effects. The two biopolymers also could stabilize as-synthesized Ag NPs. Physicochemical features of the material were further characterized over a range of advanced methods like X-ray diffraction (XRD), elemental mapping, dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and Fourier transformed infrared spectroscopy (FT-IR). TEM analysis showed the spherical-shaped nanocomposite with the mean diameter in the range of 5-15 nm. Thereafter, the nanocomposite was exploited in the anti-malignant melanoma and cytotoxicity effects studies against various human malignant melanoma cell lines (HT144, RPMI7951, SKMEL2, UACC3074, WM266-4 and MUM2C) in situ. The bio-composite corresponding IC values were 193, 102, 227, 250, 301, and 203 μg/mL against MUM2C, WM266-4, UACC3074, SKMEL2, RPMI7951, and HT144 cell lines, respectively. A significantly high IC value offered an excellent antioxidant capacity of bio-composite. According to the above results, Ag NPs/CS-Starch nanomaterial can be utilized as an efficient drug to treat malignant melanoma in humans after doing clinical trial studies.Copyright © 2023. Published by Elsevier B.V.