Background: Oxidative injury plays a pivotal impact in the development of human diseases, and it is a major component of the pathophysiology of several inflammation-linked human medical disorders. Objective: The focus of this study was to evaluate the cytotoxicity and antioxidant potential of the fruit of Lagenaria breviflora (Benth.) Roberty (LB). Methods: The antioxidant capacity of L. breviflora's crude and solvent fractions was assessed using standard techniques by measuring the total phenolic content, total flavonoid content, and DPPH radical scavenging activity. The data we0re analyzed using One-way ANOVA, and Dunnett's Multiple Comparison was used to establish the threshold. Results: The total flavonoid contents of fruit methanol extract, LB hexane, chloroform, and ethyl acetate fractions were 32.00 ± 0.94, 224.32 ±0.05, 224.06 ±0.14, and 2615.67 ± 13.20 mg gallic acid equivalent/g of extract, respectively. In contrast, the total phenolic contents were 5218.83 ± 3.18, 2615.67 ± 13.20, and 4553.00 ± 24.27 mg gallic acid equivalent/g of extract, respectively. The crude extract of LB, hexane fraction, chloroform, and ethyl acetate fraction displayed IC50 values of 242.57 ± 8.90, 262.91 ± 6.49, 96.17 ± 2.74, and 221.45 ± 0.83 μg/mL, respectively, for their ability to scavenge DPPH radicals. Ascorbic acid and rutin had IC50 values of 2.76 ± 0.01 and 20.6 ± 9.26 μg/mL, respectively. Conclusions: Fruit from L. breviflora (LB) exhibited strong antioxidant potential, which may have resulted from the fruit's phenolic and flavonoid content. This demonstrates the reason this herb is used in traditional medicine. Keywords: Oxidative stress, brine shrimp lethality assay, total phenolic contents, total flavonoid contents, DPPH, Lagenaria breviflora fruit.