Class B G-protein coupled receptors (GPCRs) are significant therapeutic recipients in cardiovascular, neurological, and metabolic diseases. The human gut microbiome is a complex microbial ecology recently identified as a possible source of bioactive peptides that control host physiological functions. Candidate peptides were found using advanced bioinformatics tools including sequence homology analysis, structure modeling, and molecular docking. These peptides were then evaluated for their binding affinity and potential functional regulation of the GPCR activity. Molecular dynamics simulations offered additional insights regarding the stability and interaction diversity of peptide-receptor complexes, highlighting receptor conformational state of G-protein interaction. The findings identify unique microbial peptides capable of influencing class B GPCR function, providing important insights into microbiome-host interactions and therapeutic potential. This study emphasizes the gut microbiome's previously untapped potential as a source of GPCR modulators, opening up new avenues for microbiome-driven therapy approaches for metabolic and endocrine disorders.