Urban residents suffer more from heat stress, compared to people living in rural areas, due to the urban heat island (UHI) effect. Mitigation of UHI is thus essential to improving human thermal comfort and living environment in urban residential areas. However, little attention has been paid to the integrated effect of UHI mitigation strategies on human thermal comfort, which is influenced by the combination of temperature, humidity, wind, and radiation. This study evaluates the effectiveness of two promising UHI mitigation strategies, cool and green roofs, in improving human thermal comfort during a heatwave in Berlin. Human thermal comfort is represented by the Universal Thermal Climate Index (UTCI), calculated by combining the Weather Research and Forecasting model coupled with the Urban Canopy Model (WRF/UCM) with the RayMan model. The results show that cool roofs outperform green roofs in reducing urban temperatures, especially at night. Besides temperature reduction, both strategies show lower wind speed, lower mean radiant temperature, and higher relative humidity. These combined effects lead to a city-scale decrease in UTCI. Cool roofs reduce more UTCI than green roofs, although they both shorten the duration of strong heat stress from 7 h d⁻¹ to 5 h d⁻¹. A higher albedo and irrigation can strengthen the cooling effect of cool and green roofs, respectively. Our study can deepen the understanding of the mechanism of natural infrastructure in improving human thermal comfort, providing scientific guidance for future city management.