Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most used pharmaceuticals in the world that introduced into the environment via hospital wastes. These drugs have been detected in many aquatic ecosystems in Egypt, such as the Rosetta Branch of the River Nile, even in drinking water. The objective of this study is to investigate the toxicological effects of ibuprofen (IBP), diclofenac (DCF), and naproxen (NPX) on the freshwater crayfish Procambarus clarkii at concentrations that are close to those in its natural environment. The experimental crayfish were exposed for 60 days and divided into 9 groups; including the control, DCF, IBP, and NPX separately or in combination with the three drugs. The used low concentrations were 0.64mg/L, 100µg/L, and 2mg/L, while high ones were 17mg/L, 63mg/L, and 15mg/L for DCF, IBP, and NPX, respectively. The eighth group of crayfish was treated with a mixer of drugs at low doses while the ninth was treated with a previous mixer co-treated with Chlorella vulgaris algae. The results showed that lipid peroxidation, nitric oxide contents, glutathione-S-transferase, aspartate transaminase, alanine transaminase, and alkaline phosphatase activities were significantly increased in the hepatopancreas of the crayfish exposed to IBP, DCF, and NPX. On the other hand, total protein, glucose, and calcium contents were significantly decreased after IBP, DCF, and NPX exposure versus the control. Biological treatment with C. vulgaris improved marginally these symptoms. Also, obvious histological damage was observed by drug treatments and slight improvement was noticed by adding algae. According to these findings, DCF, IBP, and NPX were to blame for the abnormalities in the biochemical indicators examined and the histological damage at low and high doses. While treatment with C. vulgaris adjusted the damage in the mixed low dose although this improvement was not to the level of the control.