The absence of adequate moisture resulting from drought poses a significant threat to both the viability and productivity of soybean cultivation. Genetic variation in common soybeans has been noticeably reduced through continuous breeding, and wild relatives with wider genetic diversity are one of the best tools in the search for new tolerance genes. In this study, we selected 139 genes co-expressed at transcript and protein levels in response to drought in Glycine soja through a multi-omics analysis. Drought stress induced co-expression of transcripts and proteins involved in dopamine synthesis within tyrosine metabolism. Polyphenol oxidase, involved in the dopamine synthesis process, was uniquely identified in both DEGs and DEPs, with its protein abundance increased. Co-expression of 9-lipoxygenase during linoleic acid metabolism was confirmed, along with consistent protein accumulation. The co-expression profiling of transcripts and proteins suggests that they may influence their regulatory feedback loops or unknown regulatory mechanisms. Additionally, we predicted the regulation of alternative splicing (AS) in response to drought. AS was predicted for 139 co-expressed genes, and four drought-tolerance-related gene candidate groups were selected. The expression levels of four genes, FT1, CCR1L, RPL18, and uncharacterized LOC114422617, varied depending on their transcript isoforms under drought stress. The occurrence of AS under drought stress may play a role in eliminating susceptibility genes or inducing tolerance genes to adapt to drought stress. Overall, this study reveals a novel mechanism of drought adaptation in wild soybean by predicting the regulation of metabolic pathways and AS events at the transcriptome and proteome levels and presents potential targets for soybean breeding.