Background <p>People with colorectal cancer (CRC) in the postoperative period face a high prevalence of nutritional risk and malnutrition. Oral nutritional supplementation (ONS) is the guideline-recommended primary method of nutritional support for this population; however, its effectiveness is often undermined by low compliance among them. This study sought to investigate the needs and preferences of people with CRC in the postoperative period regarding ONS, offering a theoretical foundation for enhancing compliance from the perspective of participants’ preferences.</p> Methods <p>A qualitative descriptive study was conducted, involving semi-structured interviews with 14 people with CRC in the postoperative period at a tertiary hospital in Xiamen, China, from March to April 2025. Data analysis integrated unstructured observational data with details of the oral nutritional supplements and ONS regimens used by participants, and the research team employed thematic analysis to synthesize the findings.</p> Results <p>Two primary themes emerged, encompassing seven subthemes: (1) Demands and preferences for oral nutritional supplements: Participants valued portability, practicality, standardization, scientific validity, and clear labeling; they also sought improved cost-effectiveness or reimbursement via medical insurance, rapid and significant nutritional support effects, and a preference for disease-specific formulas. (2) Demands and preferences for ONS regimens: Participants emphasized credibility, alignment with personal habits and preferences, and the provision of education and guidance.</p> Conclusion <p>People with CRC in the postoperative period reported suboptimal experiences with ONS, exhibited notable misconceptions about its use, and indicated that current regimens failed to address their treatment needs and preferences. Clinicians should adopt a person-centered approach, designing ONS regimens tailored to their preferences to improve acceptance and compliance.</p>