Among the various products of the nano industry, fullerenes occupy a special place. Fullerenes have many applications, including pharmacology, biosensors, packaging composites, plant protection products, etc. Fullerenes and their polyhydroxylated derivatives have pronounced antioxidant, hepatoprotective, radioprotective, and other types of protective action on the human body. However, the introduction into the circulation of products containing fullerenes is hindered by the ambiguity of the properties exhibited, consisting of the presence of signs of nanotoxicity for biological systems in vitro and in vivo. This study aimed to evaluate the oral toxicity of the fullerene C₆₀ and its water-soluble derivative C₆₀(OH)₂₄ at their daily doses from 0.1 to 10 mg/kg body weight (bw) in the long-term experiments on Wistar rats. According to research results, C₆₀ exhibited a general toxic effect in animals, expressed in a dose-dependent decrease in relative liver weight, impairment of barrier function of the small intestine, and an increase in the number of CD106+ granular cells in the liver parenchyma. The NOAEL for C₆₀ on oral subacute administration was at least 1 mg/kg bw/day. Negative effects of C₆₀(OH)₂₄ in animals were manifested starting from a dose of 1 mg/kg bw and consisted in an increase of adrenal mass, changes in the leukocyte blood count, including an increase of monocytes, and immature granulocytes. Based on the results, it can be assumed that the NOAEL of C₆₀(OH)₂₄ for rats in a one-month experiment is at least 0.1 mg/kg bw. Among other biological effects, it is possible to note the dose-dependent increase in the selenium content in the blood, liver, and brain of rats, which consumed C₆₀ for 92 days. Given the role of selenium compounds as indirect-acting antioxidants, there is no reason to interpret the detected effect as unfavorable. Nevertheless, the results of the toxicological assessment of fullerenes indicate the risks associated with their adverse effects on the human body when ingested and point out the necessity for the regulation of these compounds in consumer products and environmental objects.