Chlorella has long been associated with detoxification of toxic/heavy metals. It binds and eliminates different radioisotopes of strontium, technetium, uranium, cobalt, and thallium. In this context, Chlorella (C. vulgaris) powder may be of use to remove toxic metals from the body due to its adsorption properties. The present study evaluated the in vitro adsorption and in vivo removal efficiency of Chlorella powder for non-radioactive isotopes of cobalt, strontium, barium, cesium, and thallium. The adsorption efficacy was investigated in terms of weight of Chlorella, contact time, and metal ion concentration in simulated gastric (SGF) and intestinal (SIF) fluids. Langmuir and Freundlich adsorption isotherm models were fitted to determine the maximum binding capacity (MBC). Removal efficiency of Chlorella powder for strontium and thallium was evaluated in mice. The animals were administered Chlorella 500 and 1000 mg/70 kg human equivalent dose (HED). Most of the metal ions were adsorbed at equilibrium time of 180 min. The MBC of Chlorella for cobalt, strontium, barium, cesium, and thallium was found to be 10.64, 6.71, 28.57, 1.72, and 11.91 mg g−1 in water, respectively, and 1.20, 8.20, 3.62, 1.49, and 2.80 mg g−1 in SGF, respectively. In SIF, MBC of Chlorella was found to be 9.43, 1.81, and 7.75 mg g−1 for strontium, cesium, and thallium, respectively. Chlorella 500 and 1000 mg/70 kg HED showed significant reduction in whole body retention of strontium (26.05 and 46.40%, respectively) and thallium (18.06 and 38.39%, respectively). Chlorella treatment increased the excretion of strontium and thallium through feces and urine.