The seed kernels of Caesalpinia bonducella, a traditional medicinal plant in India, are widely used to treat various disorders, including polycystic ovary syndrome. The seed kernel possesses anti-bacterial properties against many pathogenic bacteria. However, their impact on Lactobacillus spp., a prominent gram-positive gut bacterium, has not been studied till date. The present study employed both in vitro and in silico methods to illustrate the effect of seed extract of C. bonducella against Lactobacillus rhamnosus GG. For this, disc diffusion assay was performed with 100, 500, and 1000 µg/ml of aqueous and methanolic seed extract against L. rhamnosus and E. coli, and the zone of inhibition was measured. While both the extracts inhibited the growth of E. coli, it did not show any zone of inhibition against L. rhamnosus. The latter possess surface layer proteins, SlpX and SlpA, which prevented the influx of the phytocompounds of C. bonducella, as demonstrated by molecular docking using Autodock Vina. Docking results showed that the binding of the phytocompounds to the SlpX and SlpA proteins was not in the active pockets. These findings conclude that C. bonducella seed kernel extracts are safe against the gut bacteria L. rhamnosus.