Coconut flesh is widely consumed in the market for its good flavor. However, a comprehensive and dynamic assessment of the nutrients in coconut flesh and their molecular regulatory mechanisms is lacking. In this study, the metabolite accumulation and gene expression of three representative coconut cultivars belonging to two subspecies were investigated using ultra performance liquid chromatography/tandem mass spectrometry. A total of 6101 features were detected, of which 52, 8, and 158 were identified as amino acids and derivatives, polyamines, and lipids, respectively. The analysis of the metabolite pathway showed that glutathione and α-linolenate were the main differential metabolites. Transcriptome data revealed significant differences in the expression of five glutathione structural genes and thirteen polyamine-regulated genes, consistent with trends in metabolite accumulation. Weighted correlation network and co-expression analyses showed that a novel geneWRKY28was implicated in the regulation of lipid synthesis. These results broaden our understanding of coconut nutrition metabolism and provide new insights into the molecular basis of coconut nutrition metabolism.