Kaempferia galanga L., Morinda citrifolia L., Morus acidosa Griff, and Momordica charantia L. are medicinal plants that are widely distributed in the Mekong Delta area of Vietnam. This study was meant to examine phytochemical constituents and evaluate the antioxidant activity of ethanol extracts from these four plants. DPPH, ABTS, RP and TAC were applied to assess their potential in vitro antioxidant activity. Drosophila melanogaster flies were experimental objects used to evaluate in vivo antioxidant activity. Based on the data analyzed, extract of the plant Momordica charantia L. was resulting in the greatest phenolic content at 64.63 ± 1.51 mg GAE/g extract and flavonoid content at 196.52 ± 5.76 mg QE/g extract. The analyzed result of antioxidant activity through ABTS, RP, and TAC methods also displayed the highest IC50 values of this plant extract, which was 60.02 ± 2.51 µg/mL, 69.64 ± 2.74 µg/mL, and 110.95 ± 1.65 µg/mL, respectively. Meanwhile, a maximum IC50 value of 168.30 ± 6.97 μg/mL, which was collected through the scavenging activity by DPPH, was introduced in the extract of Morus acidosa Griff. However, this value was insignificantly different as compared with the IC50 values of Morinda citrifolia L. extract at 172.30 ± 5.23 μg/mL and Momordica charantia L. extract at 188.20 ± 7.52 μg/mL. Under paraquat and H2O2-induced oxidative stress conditions, the adult fly, which was fed on extracts, had increased parameters of mean lifespan, 50% survival time, and maximum lifespan. These findings showed that Momordica charantia L. extract had the highest in vivo antioxidant activity among the investigated plant extracts. It could be concluded that Kaempferia galanga L., Morinda citrifolia L., Morus acidosa Griff, and Momordica charantia L., especially Momordica charantia L., are potential medicinal plants containing many antioxidant compounds.