Nickel-based nanocomposites have become an interesting research subject for developing effective antimicrobial materials that address the global challenges of antibiotic resistance and oxidative stress. This study explored the bioactivity potential of nickel-based nanocomposites integrated into a chitosan (CS) matrix. The co-precipitation approach, incorporating Tween-20, sodium tripolyphosphate (STPP), and sodium hydroxide (NaOH), has been employed to manufacture Ni@CS nanocomposites. The antibacterial activity of the Ni@CS nanocomposite was determined using an agar well technique, while its antioxidant activity was rated based on its ability to reduce DPPH radicals. The formation of Ni@CS nanocomposites was validated by detecting Ni absorption and the NiO phase according to ICSD#61544. The antibacterial efficacy showed that Ni@CS-25 had a maximal inhibition zone of 26.11 mm against B. cereus ATCC 10556. Meanwhile, the Ni@CS nanocomposite showed antioxidant activity at a moderate IC50 level. © 2026, Walailak University. All rights reserved.