YKYY017 is a SARS-CoV-2 membrane fusion inhibitor. We report efficacy and safety of inhaled YKYY017 for COVID-19 patients with mild to moderate illness from a phase 2 trial (ChiCTR2300075467). 239 patients aged 18-75 years with mostly mild COVID-19 were randomly allocated to receive aerosol inhalation of 10 or 20 mg YKYY017 or placebo once daily. The primary endpoint is the change in SARS-CoV-2 viral load from baseline to Day 4. The mean (±SE) differences in viral load change from baseline were -0.48 ± 0.27 log copies/mL (95% CI, -1.01 to 0.06) for the 20 mg group and -0.27 ± 0.27 log copies/mL (95% CI, -0.79 to 0.26) for the 10 mg group, compared to the placebo group. Viral load changes at visits other than Day 4 did not differ significantly from placebo in either the 10 or 20 mg YKYY017 groups. The time to sustained symptom recovery was shorter in the 20 mg YKYY017 group (median 117.53, 95%CI 95.33 to 141.45 hours) than in the placebo group (median 143.00, 95%CI 139.17 to 186.87 hours; HR 1.552, 95%CI 1.089 to 2.214, p = 0.0151), whereas the 10 mg YKYY017 group showed a similar but not statistically significant trend compared to placebo (p = 0.0833). The time to sustained symptom alleviation was shorter in both the 20 and 10 mg YKYY017 groups than in the placebo group. The adverse events were mostly mild to moderate. The primary outcome was not met. Following a supplementary phase 1b trial, we are planning another phase 2/3 trial using a twice-daily 20 mg YKYY017 regimen to further assess efficacy and safety.