The accumulation of cadmium (Cd) in edible plant parts and fertile lands is a worldwide problem. It negatively influences the growth and productivity of leafy vegetables (e.g., spinach, Spinacia oleracea L.), which have a high tendency to radially accumulate Cd. The present study investigated the influences of peptone application on the growth, biomass, chlorophyll content, gas exchange parameters, antioxidant enzymes activity, and Cd content of spinach plants grown under Cd stress. Cd toxicity negatively affected spinach growth, biomass, chlorophyll content, and gas exchange attributes. However, it increased malondialdehyde (MDA), hydrogen peroxide (H2O2), electrolyte leakage (EL), proline accumulation, ascorbic acid content, Cd content, and activity of antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in spinach plants. The exogenous foliar application of peptone increased the growth, biomass, chlorophyll content, proline accumulation, and gas exchange attributes of spinach plants. Furthermore, the application of peptone decreased Cd uptake and levels of MDA, H2O2, and EL in spinach by increasing the activity of antioxidant enzymes. This enhancement in plant growth and photosynthesis might be due to the lower level of Cd accumulation, which in turn decreased the negative impacts of oxidative stress in plant tissues. Taken together, the findings of the study revealed that peptone is a promising plant growth regulator that represents an efficient approach for the phytoremediation of Cd-polluted soils and enhancement of spinach growth, yield, and tolerance under a Cd-dominant environment.