Designer drugs like 2C-I and 25I-NBOMe have emerged as potent psychoactive substances, with several reports linking their consumption to severe poisoning and fatalities. However, there is limited information on their toxicity, particularly in in vivo models. In this manuscript, we evaluate the survival, developmental, and reproductive impact of these designer drugs on the model organism (). For this purpose, adult worms synchronized at the L1 stage were exposed to growing concentrations of 2C-I and 25I-NBOMe. The animal survival rate and the putative effects of the drugs on development and reproductive behavior were assessed after 24 h of exposure. A concentration-dependent decrease in animal survival was observed. 25I-NBOMe was approximately six times more toxic than 2C-I (LC values-1.368 mM for 2C-I and 0.236 mM for 25I-NBOMe). Furthermore, sublethal concentrations of both drugs delayed animal development and reduced the total progeny but not its survival. Overall, these findings underscore the developmental and reproductive risks associated with exposure to 2C-I and 25I-NBOMe, even at sublethal concentrations.