Introduction: cAMP Response Element Binding (CREB) and Brain Derived Neurotrophic Factor (BDNF) protein levels tend to be a critical mediator for the beneficial effects of diet on neurogenesis and cognitive function. Increased fruit intake has been associated with improved cognitive function. However, in Malaysia, most adolescents still haven't met the recommended intake of fruits and far less is known on how their adequacy of fruit intake can be affected to their protein levels of CREB and BDNF. Methods: A cross sectional study was done on 352 students aged 14 and 16 years old involving 11 secondary schools in Kuala Terengganu, Marang and Hulu Terengganu Districts. A validated MyUM adolescent FFQ was used for fruit intake assessment. Blood sample to determine the level of CREB and BDNF proteins. Results: A total of 53.7% of adolescents consumed an adequate intake (≥ 2 servings/day) of fruits. Serum level BDNF was significantly (p<0.001) higher in the adolescent with adequate fruit intake (389.05±204.96 pg/mL) compared with inadequate (< 2 servings/day) group (118.60 ± 49.04 pg/mL) and was correlated positively with fruit intake (r=0.62, p<0.001). The median of CREB protein level was significantly (p<0.021) higher among inadequate intake of fruits (19.85±23.60 ng/mL) relative to adequate group (14.71± 17.9 ng/mL) and was negatively correlated with fruit intake (rs (8) =-0.07, p<0.001). Apple, papaya, watermelon, orange, pear, guava, mango, banana and durian were significant factors for BDNF protein level. Conclusion: High serum protein level of BDNF in the adolescent with adequate intake of fruit could have a role in controlling neuronal survival, and synaptic function in the central nervous system.