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Background: The safety of the use of medicinal plants is a general challenge among consumers. To improve the use, it is necessary to provide complete profiles of the natural medications for quality control and the therapeutic and toxicity effects. This study was conducted to evaluate the structural and functional toxicity of the methanolic extracts of Salvia rhytidea and Glycine max plants in mice. Methods: After determining the LD50, NMRI mice with mean weight of 25-30 g were treated intraperitoneally with 100, 200 and 400 mg/kg, and orally with 800 mg/kg of the extracts for 7 consecutive days. After the last treatment, the serum samples were prepared and used for the biochemical assays. The liver and left kidney were removed from the animals and fixed in 10% formalin for histopathological examinations. Results: The results indicated that the biochemical parameters of liver and kidneys were not significantly different among the experimental and control groups (P>0.05). Mild degenerative changes in the liver and kidneys were observed at the IP dose of 400 mg/kg and oral dose of 800 mg/kg of both extracts. Conclusion: The use of these plants’ extracts did not induce severe toxicity in the short-term; however, caution should be exercised with the long-term use.