Currently, the use of medicinal plants is one of the most important biotechnological alternatives in the treatment of numerous diseases, particularly non-communicable diseases. One such plant, Cnidoscolus aconitifolius, also known as “chaya” in Mexico, is a rich source of bioactive phytochemicals. It is widely distributed across Central America and has ornamental, food, and medicinal values. Studies are needed to confirm that there are no negative effects after sustained consumption of Cnidoscolus aconitifolius. Experiments using animal models can be used to evaluate the possible chemopreventive effects of this plant against various diseases consistent with ethnobotanical information. Accordingly, a preclinical longitudinal experimental study in Sprague Dawley rats was conducted at 16 and 32 weeks' after the daily consumption of an infusion of chaya leaf. Bodyweight gain, food and beverage consumption, blood analysis, and histological analysis of the organs responsible for metabolism and excretion were evaluated. No significant differences were found between the control group and the group that consumed the chaya leaf infusion after 16 and 32 weeks. The proposed experimental model may be reliably used for research purposes to evaluate the possible effectiveness of this plant in preventing and/or treating chronic diseases.