Probiotics have shown efficacy in preventing and reducing infections caused by common viruses, including rotavirus, norovirus, hepatitis, human papillomavirus (HPV), human immunodeficiency virus (HIV), and herpes simplex virus (HSV). A randomized, double-blind, placebo-controlled, three-arm parallel-group study was conducted on 56 patients with moderate COVID-19 symptoms. Patients were randomly assigned to one of the three groups: standard treatment combined with Bacillus clausii UBBC-07, standard treatment combined with Bacillus coagulans Unique IS-2, or standard treatment with a placebo. The probiotics were administered as an oral suspension containing 2 billion spores, taken twice daily for 14 days. The placebo group received distilled water administered twice daily for 14 days. Clinical recovery and respiratory parameters were assessed, with C-reactive protein (CRP), serum ferritin, and lactate dehydrogenase (LDH) levels measured on days one, seven, and 14, while D-dimer and interleukin-6 levels were evaluated on days one and 14. There was a significant reduction (p < 0.01) in serum ferritin levels for both Bacillus clausii UBBC-07 and Bacillus coagulans Unique IS-2 compared to the placebo group. The median reduction in serum ferritin levels on day seven was 345 μg/L (39.2%) in the Bacillus clausii UBBC-07 group, 350 μg/L (40.7%) in the Bacillus coagulans Unique IS-2 group, and 270 μg/L (30.9%) in the placebo group. By day 14, the reductions were 665 μg/L (75.6%) for the Bacillus clausii UBBC-07 group, 630 μg/L (73.3%) for the Bacillus coagulans Unique IS-2 group, and 595 μg/L (69.1%) for the placebo group. D-dimer levels were significantly reduced by the end of treatment (day 14) in the Bacillus coagulans Unique IS-2 group compared to the placebo group, with median decreases of 0.36 μg/ml (60.0%) for Bacillus coagulans Unique IS-2, 0.21 μg/ml (36.8%) for Bacillus clausii UBBC-07, and 0.22 μg/ml (34.4%) for the placebo group. No significant differences were observed in other biomarkers, including CRP, LDH, and interleukin-6. No adverse effects related to probiotic administration were observed, and the intervention was well tolerated by all patients. In conclusion, Bacillus coagulans Unique IS-2 and Bacillus clausii UBBC-07 may be considered adjunct therapies for mitigating COVID-19 infections.