Ludwigia hyssopifolia and Ludwigia adscendens are two indigenous and common plant species in Vietnam with hepatoprotective property mentioned in numerous articles published in international journals. Therefore, the current paper aimed to evaluate the physicochemical parameters, total polyphenolic and flavonoid contents of the methanolic extracts from 04 parts of Ludwigia hyssopifolia and Ludwigia adscendens in Mekong delta, Vietnam. Most importantly, antioxidant properties by DPPH radial scavenging assay and antiproliferative potentials on human hepatic cancer (HepG2) cells of these multiple extracts also were determined in the in vitro models. These results showed that physicochemical parameters were within allowable limits according to the literatures. Among the investigated samples, the leaf and whole plant extract from Ludwigia hyssopifolia had the highest values of total phenolic and flavonoid contents being 196.55 ± 5.05 mg GAE/g and 64.72 ± 4.63 mg QE/g respectively. Additionally, the methanol whole plant extract of Ludwigia hyssopifolia and the methanol leaf extract of Ludwigia adscendens show the greatest antioxidant properties in DPPH scavenging assay with IC50 values of 44.48 ± 4.29 µg/mL and 26.11 ± 0.37 µg/mL respectively. Furthermore, the methanolic extract from Ludwigia hyssopifolia leaves displays the most potential anti-HepG2 activity among all surveyed samples. Therefore, the most promising extracts need further evaluation for potential herbal product developments.