THIS STUDY aimed to explore the effects of zinc oxide nanoparticles (ZnO NPs) on physiological parameters of Solanum nigrum calli and the possibility of using it as a remediator for contaminated media. In vitro experiments were conducted to understand the mechanism of S. nigrum in the remediation of ZnO NPs (0, 50 and 100 mg L-1 used). The dry weight of calli subjected to the lowest concentration of ZnO NPs was increased (1.8 fold higher than the control). The activities of lipoxygenase and antioxidant enzymes in the callus were stimulated at the highest level of ZnO NPs. The treatment of ZnO NPs did not change the activity of phenylalanine ammonia-lyase and phenolic compounds while reducing the activity of polyphenol oxidase. The contents of phosphorus and potassium were decreased under ZnO NPs treatments. Amino acids, soluble proteins, soluble carbohydrates, and Zn content were elevated in the ZnO NPs-treated-callus. The infrared spectroscopy analysis proved the differences between most macromolecules. The results indicate that this plant can be used in the remediation of ZnO NPs in the contaminated media.