Background: Antibiotic diarrhea is a frequent complication of antimicrobial therapy and is mediated mostly by interference with the normal gut microbiota. Disturbed microbial flora, and excess of pathological organisms are also causes of delayed recovery and risk of recurrence. Probiotics have been suggested as a solution that can be used to achieve microbial balance and better clinical outcomes. Objective: To evaluate the effect of probiotic supplementation on clinical recovery and gut microbiome restoration in patients with post-antibiotic diarrhea. Methodology: The proposed comparative study is a prospective study that can be carried out at Lahore General Hospital between January 2024 and January 2025. One hundred and twenty-four adult diarrhea patients who had received antibiotics in the past were recruited and randomly divided into 2 groups that included a probiotic group (n = 36) and a control group (n = 36). The intervention group got a standardized probiotic formulation of Lactobacillus and Bifidobacterium species of 1010 CFU per day of 7 days, whereas the control group got normal supportive care. Time to diarrhea resolution and stool frequency were considered as primary outcomes. Recurrence of symptoms and diversity of gut microbiome were considered secondary outcomes. A significance level of p < 0.05 was used in terms of statistical analysis. Results: The probiotic group had a significantly shorter time to diarrhea resolution compared with controls (3.2 ± 1.1 vs. 5.1 ± 1.6 days, p < 0.001). Stool frequency decreased more rapidly, and a higher proportion achieved normal stool consistency by Day 7. Recurrence of diarrhea and need for rescue therapy were significantly lower in the probiotic group. Conclusion: Probiotic supplementation significantly improves clinical recovery and promotes gut microbiome restoration in patients with post-antibiotic diarrhea.