BACKGROUND: Quercetin has recently become a remarkably popular subject of research due to its broad beneficial pharmacological properties. The goal of our study was to observe its effects on contractility of human gastric smooth muscles in reference to the NO pathway and direct influence of potassium channels. METHODS: Tissues were obtained from patients undergoing sleeve gastrectomy due to morbid obesity (n = 10 aged 24-56; BMI 47.16 ± 1.84). The following parameters were evaluated in the recordings: area under the curve (AUC), average baseline muscle tone, and relative change in muscle contraction. KEY RESULTS: Quercetin induced noticeable, dose-dependent relaxation of the carbachol treated gastric strips. The substantial effect was noted at concentrations higher than 10 mol/L and maximal at 10 mol/L (81.82 ± 3.32%; n = 10; p < 0.0001) of the control. Neither NOS blockers nor guanylyl cyclase blockers had inhibitory effects on the relaxation of strips induced by examined polyphenol. Glibenclamide inhibited the relaxing effect of quercetin, significant at concentrations higher than 5⋅10 mol/L. Preincubation with charybdotoxin or apamin extended the relaxing effect of quercetin (from 10 mol/L). Tamoxifen, in turn, significantly increased muscle relaxation at all quercetin concentrations. CONCLUSIONS & INFERENCES: In conclusion, the current study was the first to show that quercetin-induced relaxation of human gastric smooth muscle occurs directly through K channels and independently to NO pathways. The present results suggest that quercetin is a potential nutraceutical in the treatment of functional gastrointestinal dyspepsia and other minor gastric muscle motility disturbance.