Recent studies have suggested potential health risks associated with the consumption of artificial sweeteners. This study investigates the effects of the artificial sweeteners aspartame and neotame on neurobehavioral performance and selected hematological parameters in male rats. Twenty-four male albino rats, weighing 200 to 240 g, were divided into three groups: a control group receiving tap water, a group receiving neotame (250 mg/kg/day), and a group receiving aspartame (500 mg/kg/day). The study was conducted over eight weeks under controlled conditions. Neurobehavioral assessments included the open field test, swimming rank test, and Y-maze test. Hematological parameters were analyzed using an automated blood analyzer after the experimental period. The findings indicated that both aspartame (ASP) and neotame (NEO) significantly affected neurobehavioral parameters in male rats. The open field test results demonstrated a marked reduction in locomotor activity in both treatment groups compared to controls (p < 0.05).