In our life scenarios, we are involuntarily exposed to many heavy metals that are well distributed in water, food, and air and have adverse health effects on animals and humans. Cadmium (Cd) is one of the most toxic 10 chemicals reported by The World Health Organization (WHO), affecting organ structure and function. In our present study, we use one of the green microalga Chlorella vulgaris (ChV, 500 mg/kg body weight) to investigate the beneficial effects against CdCl2- induced hepato-renal toxicity (Cd, 2 mg/kg body weight for 10 days) on adult male Sprague-Dawley rats. In brief, 40 adult male rats were divided into four groups (n = 10); Control, ChV, Cd, and Cd + ChV. Cadmium alters liver and kidney architecture and disturbs the cellular signaling cascade, resulting in loss of body weight, alteration of the hematological picture, and increased ALT, AST, ALP, and urea in the blood serum. Moreover, cadmium puts hepatic and renal cells under oxidative stress due to the up-regulation of lipid peroxidation resulting in a significant increase in the IgG level as an innate immunity protection and induction of the pro-inflammatory cytokines (IL-1_ and TNF-_) that causes hepatic hemorrhage, irregular hepatocytes in the liver and focal glomeruli swelling and proximal tubular degeneration in the kidney. ChV additive to CdCl2, could organize the protein translation process via NF-kB/Nrf2 pathways to prevent oxidative damage by maintaining cellular redox homeostasis and improving the survival of and tolerance of cells against oxidative damage caused by cadmium. The present study shed light on the anti-inflammatory and antioxidative properties of Chlorella vulgaris that suppress the toxicity influence of CdCl2.This study showed that cadmium chloride altered the physiological response, including hematological and serum biochemical parameters (liver and kidney function markers), immunological and inflammatory biomarkers, and induced oxidative stress and histopathological alterations in the liver and kidney of adult male rats. On the other hand, C. vulgaris succeeded in preventing the disruption of organ functions by protecting them from oxidative stress and inflammation and enhancing immunity. These effects of C. vulgaris could be the mechanisms of their hepato-renal protection. Moreover, the beneficial role of C. vulgaris in this study could be suggestive of their use as an immunomodulatory and antioxidant supplement and could be a base for further research on its importance in detoxifying the body from environmental pollutants.