Objective. To evaluate the phytochemical content and antioxidant potential of the acetone, aqueous, and methanol extracts of the fruit, leaf, and root of Cucumis africanus L.f. Methods. Total phenolic, flavonoid, and proanthocyanidin contents were evaluated using spectrophotometric methods. The free radical scavenging activity of the acetone, methanol, and aqueous extracts of the fruit, leaf, and root were evaluated against DPPH+, ABTS+, and phosphomolybdenum. Alkaloid and saponin contents were also determined. Results. The acetone extract of the fruit revealed the highest polyphenol content when compared with the other solvent extracts analyzed. Total phenol content of the parts tested ranged from 3.66 ± 0.17 to 44.98 ± 3.41, flavonoid content ranged from 4.63 ± 3.33 to 401.33 ± 7.89, and proanthocyanidin content ranged from 8.84 ± 2.65 to 504 ± 36.6. Significant amount of alkaloids present was observed in the fruits, leaf, and root (10.68 ± 0.68, 14.12 ± 1.67, and 12.15 ± 4.74), respectively, while saponin content was 33.33 ± 11.55, 26.67 ± 11.55, and 20.00 ± 0.00 for the fruit, leaf, and root, respectively. Solvent extracts showed significant antioxidant activity, with acetone showing highest antioxidant ability in correlation with the polyphenol contents. Based on the IC50 values, acetone extract of the root revealed the best DPPH radical scavenging ability, the leaf aqueous extract had the highest IC50 value for ABTS, and the methanol extract of the leaf was best for phosphomolybdenum assays. Conclusion. This study suggests that fruit, leaf, and root of Cucumis africanus could be a potential source of natural antioxidant and justifies its use in ethnomedicine.