Grain yield is a polygenic trait that can be influenced by environmental factors and genetic compositions at all plant growth stages. Currently, the molecular mechanisms behind the coordination of the interaction between grain yield-related traits remain unknown. In this study, we characterized the function of four STRESS_tolerance and GRAIN_LENGTH (OsSGL) Poaceae ortholog genes that are transcribed into DUF1645 domain-containing proteins in relation to the grain length, grain weight, and drought stress-tolerance of rice. The transgenic plants with overexpressing or heterologous high levels of Poaceae OsSGL ortholog genes exhibited longer grain size than the wild type plants. Larger cells were seen in panicles of the four transgenic lines with paraffin sectioning and scanning electron microscopy analyses. In addition, four Poaceae OsSGL ortholog genes positively affected the drought tolerance of rice. Four transgenic plants displayed higher resistance to drought stress at the seedling and vegetative stages. RNA-sequencing and qRT-PCR results indicated that over- or heterologous-expression of four Poaceae OsSGL ortholog genes also affected the transcriptome of rice plants. These genes may play a role in auxin and cytokinin biosynthesis and their transduction pathways. Taken together, these results suggested that the four OsSGL orthologs have a conserved function in the regulation of stress-tolerance and cell growth by modulating hormonal biosynthesis and signaling.