Aims: To investigate the drug‐drug interaction (DDI) of ciprofol injectable emulsion and mefenamic acid capsules in healthy subjects. Methods: Twenty healthy subjects were enrolled in this single‐centre, open‐label, two‐period DDI study. Ciprofol (0.4 mg kg−1) was administered as a single dose on days 1 and 5. A 500‐mg oral loading dose of mefenamic acid was given on day 4 followed by a 250‐mg maintenance dose every 6 h (a total of eight doses). Blood samples for pharmacokinetic analyses were collected. Depth of anaesthesia was monitored using the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scale and Bispectral Index scores (BISs). Results: Compared with administration of ciprofol alone, administration with mefenamic acid showed no significant difference in exposure. The geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) for maximum plasma concentration (Cmax), area under the plasma concentration‐time curve calculated from 0 to the last measurement point (AUC0‐last) and AUC to infinity (AUC0‐inf) were 91.6% (86.5‐96.9%), 103.3% (100.3‐106.4%) and 107.0% (101.2‐113.2%), respectively. The MOAA/S and BIS curves for the two treatment periods essentially coincided, indicating that the anaesthesia effect of ciprofol was not affected by mefenamic acid. Seven subjects (35%) reported eight adverse events (AEs) when ciprorol was administered alone and 12 subjects (60%) reported 18 AEs when ciprofol was administered in combination with mefenamic acid. All AEs were mild. Conclusions: Mefenamic acid, a UGT1A9 inhibitor, had no significant effect on the pharmacokinetics and pharmacodynamics of ciprofol in healthy subjects. Ciprofol was safe and well tolerated when administered with mefenamic acid. [ABSTRACT FROM AUTHOR]