Objective To improve the sensitivity and broaden the applicability of N-of-1 trials in traditional Chinese medicine (TCM), the clinical application and methodology of single-case experimental designs (N-of-1trials, multiple-baseline designs; MBDs) were expounded, compared, and discussed. Methods This paper introduced the current utility of N-of-1 trials in TCM research, introduced MBDs, and compared the methodologies of N-of-1 trials, MBDs and crossover design. Finally, two design schemes to improve the sensitivity and applicability of N-of-1 trials were illustrated. Results N-of-1 trials conformed to the TCM concept of treatment based on syndrome differentiation; however, due to the complex composition of TCM, the results were easily affected by carryover effect. In MBDs, the intervention was introduced in a staggered way, no washout period was needed, and the required sample size was small. MBDs were generally used to preliminarily indicate the effect of intervention; however, the statistical analysis was relatively complicated, and there were few MBDs used in clinical trials of TCM at present. Compared with crossover trials, single-case experimental designs had advantages and disadvantages. N-of-1 trials might best reflect the individualized treatment of TCM and a suitable statistical model (e.g., hierarchical Bayesian statistical method) was expected to improve the sensitivity and applicability of N-of-1 trials in TCM. Combining clinical trial designs (e.g., the combination of N-of-1 trials and MBDs) would complement the limitations of N-of-1 trials, and expand the scope of conditions applicable for study. Conclusion N-of-1 trials have both advantages and disadvantages in TCM research. Improved statistical models or combined study designs will improve the sensitivity and broaden the applicability of N-of-1 trials in TCM.