Cadmium (Cd) is one of the dominant metal pollutants present in the aquatic environment that affects ion homeostasis, oxidative stress (OS) and immune responses of aquatic organisms. Given the physicochemical similarities between Cd²⁺ and calcium (Ca²⁺) ions, their antagonism may facilitate the mitigation of Cd-induced toxicity. To better understand the role of Ca in protecting against Cd-induced toxicity in teleosts, juvenile grass carp were exposed to Cd (measured concentration 3 μg/L) and a gradient of Ca concentrations (measured concentration 1.5 mg/L, 2.5 mg/L, 3.0 mg/L, and 3.5 mg/L in the control (CTL) group, low calcium (LCA) group, medium calcium (MCA) group, and high calcium (HCA) group, respectively) for 30 days. Inductively coupled plasma mass spectrometry (ICP-MS) data analyses showed that simultaneous exposure to Ca impaired the accumulation of Cd in all tested tissues. Besides, Ca addition maintained the plasma ion (Na⁺, K⁺, Cl^-) homeostasis, alleviated Cd-induced oxidative stress (OS), and regulated the activities and transcriptional levels of ATPase. Furthermore, transcriptional heatmap analysis demonstrated that several indicator genes for OS and calcium signaling pathway were found to be significantly modulated by Ca addition. This work delineates a protective effect of Ca against Cd-induced toxicity in grass carp, providing new insight into the possible solutions to Cd pollution issues in aquaculture industry.