Tubby-like proteins, which are encoded by large multigene families in plants, play important roles in abiotic stress tolerance; however, it is still unclear how they work in rice during herbicides stress. In order to address this gap, we looked into the traits and roles of genes encoding tubby-like proteins in rice plants (Oryza sativa; hereafter referred to as OsTLP genes) exposed to two herbicides, anilofos and bentazone. Transcriptome analysis revealed 7 genes encoding tubby-like proteins. Quantitative reverse-transcription PCR confirmed that the expression of 6 and 4 TLP genes was enhanced under anilofos- and bentazone-induced stress, respectively. Seven genes were found to be unevenly distributed over five of the twelve chromosomes, with segmental duplication playing a role in the growth of gene families, according to chromosomal mapping. According to a collinearity research, rice and other plant species have the following orthologous gene pairs: 17 with sorghum (Sorghum bicolor), 0 with Arabidopsis (Arabidopsis thaliana), 11 with maize (Zea mays), and 7 with soybean (Glycine max). These genes were divided into three clades by phylogenetic analysis. According to structural study, TLP genes have a variety of conserved domains, motif compositions, cis-acting elements, and designs that allow them to respond to both biotic and abiotic stress. Analysis of protein–protein interaction networks further showed that tubby-like proteins may contribute to anilofos and bentazone metabolism. According to in silico predictions of subcellular localization, all seven TLP genes’ encoded proteins are found in the nucleus. Docking analyses identified important amino acid residues implicated in pesticide binding between tubby-like proteins and the two herbicides (anilofos and bentazone). These results shed light on the TLP gene superfamily and provide useful resources for functional research on these genes’ functions in herbicides metabolism.