In recent years, shoes having rounded soles in the anterior-posterior direction have been commercially introduced, which are commonly known as unstable shoes (US). However, physiological responses during walking in US, particularly at various speeds, have not been extensively studied to date. The purpose of this study was to investigate the effect of wearing unstable shoes while walking at low to high speeds on the rate of perceived exertion (RPE), muscle activation, oxygen consumption (VO₂), and optimum speed. Healthy male adults wore US or normal walking shoes (WS), and walked at various speeds on a treadmill with no inclination. In experiment 1, subjects walked at 3, 4, 5, 6, and 7 km·h^-1 (duration, 3 min for all speeds) and were recorded on video from the right sagittal plane to calculate the step length and cadence. Simultaneously, electromyogram (EMG) was recorded from six different thigh and calf muscles, and the integrated EMG (iEMG) was calculated. In experiment 2, RPE, heart rate and VO₂ were measured with the walking speed being increased from 3.6 to 7.2 km·h^-1 incrementally by 0.9 km·h^-1 every 6 min. The optimum speed, defined by the least oxygen cost, was calculated from the fitted quadratic relationship between walking speed and oxygen cost. Wearing US resulted in significantly longer step length and lower cadence compared with WS condition at any given speed. For all speeds, iEMG in the medial gastrocnemius and soleus muscles, heart rate, and VO₂ were significantly higher in US than WS. However, RPE and optimum speed (US, 4.75 ± 0.32 km·h^-1; WS, 4. 79 ± 0.18 km·h^-1) did not differ significantly between the two conditions. These results suggest that unstable shoes can increase muscle activity of lower legs and energy cost without influencing RPE and optimum speed during walking at various speeds.