Insects are considered as an alternative in vivo model for evaluating various biological activities. Among them, larvae stand out as experimental model due to the low economic value during maintenance, in addition to the low demand and easy handling. Tenebrio molitor larvae are receiving attention as alternative methods in determination of efficacy studies. Therefore, the present study aimed to review experimental models that use T. molitor larvae as alternatives in defining the biological activities, safety, and effectiveness of new drugs. The current review was conducted using online journal databases: PubMed, Web of Science, and Embase without geographical, publication date, or filtering restrictions. The search obtained a total of 5781 documents which were evaluated according to the focus of the review, reaching 14 articles. Thus, the systematic search strategy was developed to encompass all published papers that explore the use of larvae in experimental studies, particularly those investigating the biological activity and/or characterization of drugs/compounds. The selected articles were classified according to the methodologies used, such as toxicity, antimicrobial, and other types of assessments. Despite the results, there is still a lack of studies that use this model as a source for evaluating drugs and possible therapies.