Scientific evidence on the pharmacological and toxicological effects of Luffa operculata has been produced on a smaller scale, even though the species: (i) is edible
(ii) widely recognized in folk medicine for treating sinusitis and inducing abortion
(iii) and the basis of allopathic and homeopathic medicines. In this sense, the objective of this review is to characterize the pharmacological, toxicological and clinical profile of products based on L. operculata. After consulting 14 databases, as well as a free search on Google/Google Scholar and checking references, 85 studies were selected that met our eligibility criteria. After analysis and synthesis, we found that the products have a wide range of pharmacological activities in vitro, ex vivo and in vivo. The toxicological spectrum is also alarming in different segments such as: cytogenotoxicity, tissue toxicity, (sub-) acute, reproductive, neuro- and phytotoxicity. The intensity of the pharmacological and toxicological effects is variable, and seems to be conditioned by various factors (examples: plant organ, polarity of the extracting solvent, quantity, experimental model and route of administration). Clinical data show that the products have satisfactory efficacy, tolerability and safety in the treatment of upper airway diseases (especially rhinitis and sinusitis). Finally, we hope that the presentation of toxicological information in this review can guide the safe and rational use of L. operculata in folk medicine. It may also serve as scientific evidence for exploring the pharmacological potential of the species, avoiding its side effects.