Knee osteoarthritis (OA) is a degenerative disease which is expected to become one of the leading causes of disability by the next years. This work aims to assess if balneotherapy and spa therapy can significantly improve Quality of Life (QoL) of patients with knee OA. Medline via PubMed, Scopus, Web of Science, Cochrane Library, and PEDro were systematically searched for articles about trials involving patients with knee OA and measuring the effects of balneotherapy and spa therapy on study participants’ QoL with validated scales. A qualitative and quantitative syntheses were performed. Seventeen studies were considered eligible and included in the systematic review. Fourteen trials reported significant improvements in at least one QoL item after treatment. Ten studies were included in quantitative synthesis. When comparing balneological interventions with standard treatment, results favored the former in terms of long-term overall QoL [ES = − 1.03 (95% CI − 1.66 to − 0.40)]. When comparing balneological interventions with sham interventions, results favored the former in terms of long-term pain improvement [ES = − 0.38 (95% CI − 0.74 to − 0.02)], while no significant difference was found when considering social function [ES = − 0.16 (95% CI − 0.52 to 0.19)]. In conclusion, even though limitations must be considered, evidence shows that BT and spa therapy can significantly improve QoL of patients with knee OA. Moreover, reduction of drug consumption and improvement of algofunctional indexes may be other beneficial effects. Further investigation is needed because of limited available data.