This study presents the first comprehensive analysis of the chemical composition and bioactive compounds of Opuntia ficus-indica fruits cultivated in Ninh Thuan province, Vietnam in 2024. Key findings include a free acid content of 136.7 ± 5.77 mEq/kg, mineral content of 21.8 ± 0.05 %, total sugar content of 10.7 ± 0.06 %, reducing sugar content of 10.48 ± 0.1 %, lipid content of 1.624 ± 0.02 %, protein content of 1.619 ± 0.04 % and crude fiber content of 2.53 ± 0.06 %. These values indicate their potential as a nutrient-dense food source. In addition, the extraction of bioactive compounds was optimized using response surface methodology (RSM). Under the optimal conditions of 59.13 °C, 96.43 min and a liquid-to-material ratio of 46.5 mL/g, the total phenolic content (TPC) and total flavonoid content (TFC) reached 15.355 ± 0.028 mg gallic acid equivalents (GAE)/g dry weight (DW) and 2.404 ± 0.0428 mg quercetin equivalents (QE)/g DW, respectively. The polynomial models applied were shown to be effective in predicting and maximizing yields. Overall, the findings underscore the nutritional richness and bioactive potential of O. ficus-indica fruits, offering a scientific basis for their development into functional foods and nutraceuticals. This work provides novel insights into the value-added utilization of cactus fruits from Vietnam, contributing to both human health promotion and sustainable agricultural practices.