The current study aims to explore the anti-inflammatory activity of Chlorella pyrenoidosa on RAW 267.4 cells and followed by a cross-over clinical trial in healthy subjects to check the antioxidant and anti-aging properties of Chlorella water extract (CWE).For the clinical trial, 44 healthy subjects were requested to consume 27 ml of either placebo or CWE for 90 days (phase I) and vice-versa manner for 90 days (phase II) with 4 weeks of washout period. The RAW 264.7 macrophages treated with Chlorella display potent anti-inflammatory activity by significantly downregulating (p < .05) the protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Whereas, the subjects supplemented with CWE showed improved (p < .05) antioxidant status (TEAC, SOD, CAT, and DHEAs) and lower (p < .05) oxidative stress/aging markers (TBARS and 8-OHdG) as well as considerably (p < .05) protected liver (by lowering GOT and GPT). Thus, consumption of chlorella could significantly improve the overall health status by suppressing various oxidative stress markers and aging stress markers.