In this study, the effects of Opuntia ficus-indica lectin (OfiL) on the survival and nutritional parameters of Sitophilus zeamais (maize weevil) adults were evaluated. OfiL was incorporated into the artificial diets at concentrations of 15, 60, and 95 mg/g (mg of lectin per g of wheat flour). Mortality was evaluated after 7 and 15 days, and the amount of food ingested and the weight of the insects were determined on the 7th day. In addition, the in vitro effects of OfiL on the gut enzymes of the insect were investigated. The ingestion of OfiL did not show any significant difference in the mortality rates compared to control. The relative consumption rate was also similar to that of the control, and no deterrent effect was detected. However, the values of the relative biomass variation and the efficiency of ingested food conversion were negative in the treatments at 60 and 95 mg/g, showing that lectin ingestion resulted in weight loss. OfiL exhibited a stimulatory effect on the protease activity from S. zeamais gut extract, which may cause uncontrolled hydrolysis of proteins in the digestive tract. This lectin did not promote significant alteration in the amylase activity. In conclusion, OfiL was able to exert anti-nutritional effects without causing a deterrent effect.