The grain size and shape of rice are limited by the growth of the spikelet hulls and are important selective target during domestication and breeding. In this study, we identified a glycine- and proline-rich protein (OsGPRP3), which belongs to a conserved family rarely studied. We found that OsGPRP3 was highly expressed in the seed at 10 days after pollination (DAP) using qRT-PCR, pOsGPRP3::GUS and in situ hybridization. Knockout and knockdown of OsGPRP3 led to significant decrease of 1000-grain weight, grain width, and grain thickness. We further found that the content of storage protein and total lipid were decreased in osgprp3 lines. In particular, the contents of C14:0 (myristic acid), C16:0 (palmitic acid), C18:1 (oleic acid), and C18:2 (linoleic acid) were reduced in osgprp3 lines. Cytological experiments revealed that the cell width of spikelet hull in osgprp3 lines was significantly reduced than that in WT. Taken together, our results reveal that OsGPRP3 regulates the grain size and shape of rice by influencing the cell width of spikelet hulls and the accumulation of storage protein and lipids.