The slippery mucus produced by fish skin is important to protect fish against predator attack, allowing fish to swim faster and remain elusive because of the ultra-low coefficient of friction (COF) of fish skin. To mimic this slick skin, responsive hydrogels that respond to external stimuli, including pH and temperature, were prepared. These hydrogels were found to perform better than fish skin: not only was an ultra-low COF achieved but multiple tunable COFs from ultra-low to ultra-high were discovered using sequential regulation of pH and temperature. The tunable COF was achieved through conformational changes in the molecular chains in the responsive hydrogel that were induced by the external stimuli. Swelling of both pH-and thermal-responsive polymer chains of the hydrogel resulted in an ultra-low COF; the pH-responsive component, shrink as a result of dehydration caused by a pH change, led to a moderate COF, whereas the two components simultaneous shrink brought out a very high COF. The three levels of COF under different states can be reversibly switched multiple times by sequential regulation of pH and temperature. This reversible tunability in friction performance is likely to have a significant impact on the design of hydrogel-based actuation devices.