The use of sewage sludge (SS) in agriculture is a global practice and a unique method of waste management. SS is high in organic matter and fertilizing elements, making it a viable alternative to chemical fertilizers and of significant economic value. To investigate the impact of SS in potato (Solanum tuberosum L.) cropping systems, a pot experiment was conducted with three treatments: one with SS and another with the chemical fertilizer NPK (15-15-15) in comparison to the control, to assess the physiological and biochemical responses of the potato by characterizing its defense strategy in the face of the abiotic constraint present in the environment. Unlike carotenoids, Sewage sludge (SS) reduced chlorophyll and protein content. Furthermore, elevated levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) were detected, indicating oxidative stress. Increases in reduced glutathione (GSH) and the activities of the antioxidant enzymes catalase (CAT), ascorbate peroxidase (APX), glutathione peroxidase (GPX), and glutathione-S-transferase (GST) suggest that defense mechanisms are activated in response to this stress. The findings indicate that SS fertilization may be a viable option for potato plants because they exhibit an adaptive strategy in response to induced stress, as evidenced by increased carotenoids and GSH content, as well as various antioxidant levels.