This work investigated the protective effects of microalgaHalamphorasp. extract (HExt), a nutraceutical and pharmacological natural product, on human lead-intoxicated liver and kidney cells in vitro and in vivo in Wistar rats. The human hepatocellular carcinoma cell line HepG2 and the human embryonic kidney cell line HEK293 were used for the in vitro study. The analysis of the fatty acid methyl esters in the extract was performed via GC/MS. The cells were pretreated with HExt at 100 µg mL−1, followed by treatment with different concentrations of lead acetate, ranging from 25 to 200 µM for 24 h. The cultures were incubated (5% CO, 37 °C) for 24 h. Four groups, each containing six rats, were used for the in vivo experiment. The rats were exposed to subchronic treatment with a low dose of lead acetate (5 mg kg−1b.w. per day). Pretreating HepG2 and HEK293 cells with the extract (100 µg mL−1) significantly (p< 0.05) protected against the cytotoxicity induced by lead exposure. For the in vivo experiment, the biochemical parameters in serum—namely, the level of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)—were measured in the organ homogenate supernatants. HExt was found to be rich in fatty acids, mainly palmitic and palmitoleic acids (29.464% and 42.066%, respectively). In both the in vitro and in vivo experiments, cotreatment with HExt protected the liver and kidney cell structures and significantly preserved the normal antioxidant and biochemical parameters in rats. This study discovered the possible protective effect of HExt, which could be beneficial for Pb-intoxicated cells.