Diclofenac sodium (DFS) is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, inflammatory disorders, and dysmenorrhea but liver and kidney problems are the main worries of the agent. This study aims to highlight the possible hepatic and nephroprotective effects of Spirulina platensis (SP) on DFS-exposed rats. Forty male rats were divided randomly into four equal groups (10 each). The control group; rats received normal saline; SP group: rats received SP orally 200 mg/kg b.wt dissolved in distilled water for 7 days; the DFS group: rats received DFS orally 5 mg/kg b.wt dissolved in distilled water for 7 days; the DFS + SP group received 5 mg /kg b.wt DFS with 200 mg/kg SP for 7 days. Serum samples were collected at the end of the experiment for evaluation of liver and kidney functions, and liver and kidney tissues were collected for histopathological examination. The results revealed that DFS administration of one week showed a significant increase in ALT and AST enzyme activities, a significant decrease in albumin concentration, and a significant increase in the levels of creatinine, urea, and uric acid when compared to the control group. However, concurrent oral administration of SP with DFS exhibited a moderate ameliorating effect against DFS hepatotoxicity and a powerful nephroprotective effect as shown in the biochemical evaluations and confirmed with the histopathological examination. Therefore we can conclude that Spirulina platensis has a more powerful nephroprotective effect than hepatoprotective effect against NSAID as diclofenac sodium used in the current study.