Cytochrome P450 (CYP74) family members participate in the generation of oxylipins and play essential roles in plant adaptation. However, the metabolic reprogramming mediated byCYP74sunder cold stress remains largely unexplored. Herein, we report how cold-triggeredOsHPL1, a member of theCYP74family, modulates rice metabolism. Cold stress significantly induced the expression ofOsHPL1and the accumulation of OPDA (12-oxo-phytodienoic acid) and jasmonates in the wild-type (WT) plants. The absence ofOsHPL1attenuates OPDA accumulation to a low temperature. Then, we performed a widely targeted metabolomics study covering 597 structurally annotated compounds. In the WT andhpl1plants, cold stress remodeled the metabolism of lipids and amino acids. Although the WT andhpl1mutants shared over one hundred cold-affected differentially accumulated metabolites (DAMs), some displayed distinct cold-responding patterns. Furthermore, we identified 114 and 56 cold-responding DAMs, specifically in the WT andhpl1mutants. In conclusion, our work characterized cold-triggered metabolic rewiring and the metabolic role ofOsHPL1in rice.