Aim: Neurotoxicity is the next common side effect of cisplatin (CDDP)-based chemotherapeutics following nephrotoxicity. We investigated the effect of CDDP on some brain metabolic enzyme activities such as hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PD), lactate dehydrogenase (LDH), and malate dehydrogenase (MDH) in an experimental model of CDDP toxicity, and examined the protective role of Caffeic acid phenethyl ester (CAPE), a phenolic antioxidant derived from the honeybee propolis, on the enzyme activities mentioned above. Methods: Female Wistar albino rats were divided into three groups: sham operation group (n:6), CDDP group (n:9), and CAPE + CDDP group (n:8). All the chemicals used were applied intraperitoneally. HK, G6PD, LDH, and MDH activities were determined spectrophotometrically in the brain supernatant at the end of the surgical procedures. Results: There were decreased G6PD activities and increased MDH activities in CDDP group compared to control group (p<0.05, p<0.05). LDH activities were increased in CAPE+CDDP group compared to CDDP group (p<0.001). Conclusion: These results provide a new point of view on the glucose metabolizing enzymes of brain tissue affected from CDDP and the protective effects of CAPE on these enzymes.