Nipa palm vinegar (NPV) made from the sap of nipa palm (Nypa fruticans Wurmb.) has long been used as a local food seasoning and folk medicine. This study compared the bioactive compounds, antioxidant, in vitro anti-inflammatory and antimicrobial activities of three NPVs obtained from different plantations based on varied soil and water salinity levels, including fresh water NPV, brackish water NPV and saline water NPV. The analysis results revealed that total phenolic content of saline water NPV had statistically significantly lower than both fresh water and brackish water NPV (p < 0.0001). Furthermore percentage of acetic acid in brackish water NPV had statistically significantly lower than both fresh water and saline water. NPV (p = 0.002). Nevertheless, total flavonoid and pH, were not significantly different (p = 0.144 and 0.066, respectively). The antioxidant activities using three ABTS, DPPH and FRAP methods displayed similar patterns, in which saline water NPV showed the highest antioxidant activities, followed by brackish water and fresh water NPV, respectively. Antimicrobial activity was examined for seven enteropathogenic bacteria. The tested NPVs were found inhibitive against all test cultures with a minimum inhibitory concentration (MIC) of ≤ 7.8 µL/mL. The cytotoxicity of the NPV obtained from different plantations by MTT assay revealed low cytotoxicity. Anti-inflammatory activity was also carried out through the inhibition of nitric oxide production. The fresh water NPV exhibited the highest anti-inflammatory activity with IC50 17.59 ± 0.17 µL/mL, followed by saline and brackish water NPV with IC50 18.12 ± 0.49 and 28.29 ± 2.64 µL/mL, respectively. The findings indicated that NPV from different soil salinities could potentially be natural functional food and developed to antimicrobial and anti-inflammatory medicinal agents with safety.