The objective of this work was to evaluate the antioxidant and antityrosinase activities of Gac (Momordica cochinchinensis) extract and to clinically evaluate a Gac-containing antiwrinkle cream formulation. Gac extract exhibited higher antioxidant activity than vitamin C or E, as measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH, 41.25 ± 0.34 mg TEAC/ml extract), 2, 2'-azinobis 3-ethylbenzothialine-6-sulfonic acid (ABTS, 47.70 ± 0.18 mg TEAC/ml extract), and ferric reducing antioxidant power (FRAP, 105.03 ± 2.326 mg TEAC/ml extract) scavenging. The antioxidant activity of Gac extract was 5.85- and 11.75-fold higher than that of vitamin E in the DPPH and ABTS assays, respectively. The FRAP assay indicated that the antioxidant activity of Gac extract was 2.91-fold higher than that of vitamin C. Gac extract also exhibited high tyrosinase inhibition (62.83% ± 1.99%). The tyrosinase inhibition activity of Gac extract was 1.51- and 2.06-fold greater than that of vitamins C and E, respectively. The safety and efficacy of the formulated Gac extract cream as an antiwrinkle agent and its promotion of skin moisturization and smoothness were investigated. Evaluation of acute skin tolerance indicated nonirritating properties. A clinical study revealed increases in cutaneous hydration. Average roughness was decreased, while smoothness was increased. Skin overlook analysis indicated skin roughness relief. These results indicate that the formulated Gac extract product is an effective antiwrinkle cream.