Over the last two decades, a plethora of disease models and human studies have confirmed the beneficial effects of molecular hydrogen (H2), a simple biotherapeutic gas. Recent small-scale studies evaluating the effects of hydrogen-rich water (HRW) on various metabolic conditions pointed to advantageous effects of HRW in regulating blood lipid profiles. However, to the best of the authors’ knowledge, no systematic review and/or meta-analysis (SRMA) were published considering HRW consumption and lipid/lipoprotein status. Therefore, the aim of this SRMA was to assess the effects of HRW consumption on blood lipid panel in clinical populations. The search strategy was designed using PRISMA guidelines, and the databases PubMed/Medline, Web of Science, and Scopus were explored from inception until 4 October 2022. A total of seven studies satisfied all the eligibility criteria and were included in SRMA. The results for the pooled meta-analysis showed a significant reduction in total cholesterol, low-density lipoprotein, and triglycerides after HRW intake (p = 0.01), with small to moderate effects (pooled SMD = −0.23 (from −0.40 to 0.05); pooled SMD = −0.22 (from −0.39 to 0.04); pooled SMD = −0.38 (from −0.59 to 0.18), respectively). Our findings indicate that drinking HRW can significantly improve lipid status in the clinical populations. Additional studies are warranted to further validate this connection.