The eco-stoichiometry of Ca/Cd in soil significantly affects Cd uptake and accumulation by plants in carbonate regions. In this study, the physiological responses and detoxification mechanisms of Capsicum annuum L. (capsicum) were investigated based on the eco-stoichiometric relationship of Ca/Cd in production substrates under varying pH levels (5, 6, and 7). The results revealed that increased Ca/Cd ratio enhanced the Cd accumulation in roots at pH values of 5 and 6. The enrichment of Cd in stems and leaves gradually decreased with varying Ca/Cd ratios at different pH levels. In addition, root vigor, relative chlorophyll content, biomass, and catalase and peroxidase activities increased across various pH levels, while the concentration of protein carbonyl and malondialdehyde decreased. The ability of pectin and cellulose in the cell wall and that of soluble components within the cell to adsorb and partition Cd improved as the Ca/Cd ratio increased at different pH values. Notably, the effects of varying Ca/Cd ratios were most significant at pH 6. Overall, Ca enhanced the tolerance of capsicum to Cd stress, thereby promoting the fixation of Cd in root cells, reducing its transfer to aboveground tissues, and improving both the growth and antioxidant stress response. The effect was attributed to different Ca/Cd stoichiometric ratios, pH levels, and their interactions. These findings enhance the understanding of the mechanism of the interaction between Ca and Cd on crops in the karst agroecosystem.