Plants undergo significant abiotic and biotic stresses, resulting in heightened formation of reactive oxygen species (ROS) that can oxidize cellular components and disrupt physiological functioning. In response, plants have evolved intricate antioxidant systems, comprising enzymes and non-enzymatic substances, to neutralize reactive oxygen species and avert oxidative damage. This research assessed the antioxidant, antibacterial, and antifungal properties of C. setosum leaf extracts. Cyphostemma setosum (Roxb.) is a succulent climber clothed with scattered grandular bristly hairs; it is belonging to the family Vitaceae. The antioxidant activity was evaluated by the DPPH and phosphomolybdenum tests. In the DPPH experiment, Vitamin C exhibited the maximum activity (98%) at 80 µg/ml, succeeded by methanol (92%), chloroform (82%), and petroleum ether extracts (72%), while ethyl acetate extract displayed the lowest activity (48%). The phosphomolybdenum experiment indicated that Gallic Acid and Ascorbic Acid serve as standards with elevated total antioxidant capacities (TACs) of 92% and 85%, respectively. The methanol extract exhibited the highest total antioxidant capacity (TAC) among plant extracts at 82%, followed by chloroform at 73%, petroleum ether at 62%, and ethyl acetate at 59%, underscoring the significance of solvent polarity in antioxidant extraction. The methanol extract demonstrated the highest antibacterial activity against Pseudomonas fluorescens, E. coli, Staphylococcus aureus, and Bacillus subtilis, exhibiting inhibition zones of 8-9 mm, followed by petroleum ether (6-7 mm), chloroform (5-7 mm), and ethyl acetate (3-6 mm). Ampicillin exhibited enhanced antibacterial efficacy, with inhibition zones ranging from 8 to 15 mm. Correspondingly, the antifungal efficacy against F. oxysporum, S. rolfsii, and P. infestans demonstrated that the methanol extract was the most potent, with inhibition rates of 60%, 52%, and 60%, respectively. Chloroform, ethyl acetate, and petroleum ether extracts demonstrated moderate efficacy, but the fungicide Fluconazole exhibited inhibition rates of 50-55%. The findings highlight the potential of methanol extracts of C. setosum as a substantial source of natural antioxidants, antibacterial, and antifungal agents, positioning it as a prospective candidate for health and functional food applications.