Phytohormones are crucial in the regulation of plant growth and development, and in responses to adverse environments. Multiple cytochrome P450 monooxygenases (CYP450s) are involved in the biosynthesis and catabolism of phytohormones. Here, we report that a CYP450 member of the CYP71 clan in rice, OsCYP71D8L, participates in the control of multiple agronomic traits and abiotic stress responses by affecting gibberellin (GA) and cytokinin (CK) homeostasis. The gain-of-function mutant cyp71d8l and transgenic plants overexpressing CYP71D8L (CYP71D8L-OE) display similar phenotypes compared to the wild-type (WT), including dwarfed plants, reduced panicle length, reduced grain number per panicle, and decreased levels of endogenous GAs. Moreover, the dwarfed plant trait and the less-developed roots of CYP71D8L-OE and cyp71d8l seedlings could be rescued by application of GA3 or the CK biosynthetic inhibitor lovastatin, and exacerbated by application of the synthetic CK 6-BA. Importantly, CYP71D8L-OE and cyp71d8l seedlings maintained high chlorophyll contents and low levels of reactive oxygen species, and showed enhanced tolerance to drought and salt stress compared with the WT. Thus, our results suggest that OsCYP71D8L plays important roles in regulating rice growth and stress responses by coordinating the homeostasis of GAs and CKs, and it may therefore be a useful target for engineering stress-tolerant rice varieties.