Background <p>The quality of colonoscopy is significantly influenced by the effectiveness of bowel preparation. In this study, we aimed to evaluate the efficacy, safety, and tolerability of bowel cleansing between a new oral sulfate solution (OSS) and standard polyethylene glycol electrolyte powder (PEG).</p> Methods <p>This single center, randomized, superiority study recruited 679 outpatients who were assigned to either the new OSS group (Group A) or standard PEG group (Group B). The quality of bowel cleansing was evaluated using the Boston Bowel Preparation Scale (BBPS) and compared between the two groups. Furthermore, data pertaining to the duration of bowel preparation, patient tolerability, and the occurrence of adverse events were also analyzed.</p> Results <p>According to BBPS scores, group A demonstrated significantly higher bowel preparation cleanliness than group B. Additionally, group A achieved superior bowel cleansing, as evidenced by a greater proportion of patients with BBPS scores ≥ 8 compared to group B (75.3% vs. 55.2%, <i>P</i> &lt; 0.05). No severe adverse events were reported during examinations in either group.</p> Conclusions <p>The magnesium sulfate, sodium sulfate, and potassium sulfate concentrated oral solution is a novel, safe, and effective bowel preparation for colonoscopy.</p> Trial registration <p>This study was registered in the Chinese Clinical Trial Registry on 20/02/2024 (clinical trial registration number: ChiCTR2400081004).</p>