Summary: Polymethylsiloxane polyhydrate (PHPS), which has been used for nearly 30 years as an OTC drug, and therefore with proven safety, has undergone a series of studies confirming its in vitro activity and clinical efficacy in accordance with modern requirements of reliability-based medicine. In this study, the adsorbent activity of PHPS, compared to activated charcoal (WA), against bacterial toxins, bile acids and some drugs was found to be high, although lower than that of WA. In a randomized clinical trial, PHPS + standard DPN rehydration vs. rehydration alone resulted in a significant reduction in the duration of diarrhea and associated abdominal pain. PHPS was shown to reduce the duration of diarrhea, assessed as the time from randomization to the first non-watery stool (27.1 vs. 38.9 hours), as well as the duration of diarrhea from randomization to the last watery stool ( 25.5 hours vs. 38.4; p = 0.002), reduced the severity of abdominal pain (HR 1.74, 95% CI 1.05 to 2.8, p = 0.003), which was assessed overall as a 64% chance that diarrhea would resolve sooner after PHPS. In a randomized, double-blind clinical trial evaluating the efficacy of PHPS versus placebo in diarrheal irritable bowel disease (IBS-D), it proved to be a significantly effective drug, assessed as the so-called “treatment response” percentage (primary endpoint) (37.4% vs. 24.3% OR 1.95, NNT 8, p = 0.002). In addition, the following were found to be significantly statistically significant: pain relief, improvement in stool consistency, reduction in the number of stools and urgency to defecate, and the need for rescue loperamide. The quality of life of IBS-QoL patients also improved and the so-called IBS-SSS severity score decreased. PHPS deserves an important place as an additional drug to reduce the severity of IBS-D symptoms.