In various workplaces, gloves are commonly employed to protect the hands with the design rationale of 'the thicker the gloves, the better the protection'. Therefore, the present paper investigated the effects of glove thickness on hand performance and fatigue during two infrequent high-intensity gripping tasks, such as 5-s and sustained tasks. The hand performance was evaluated by maximum volitional contraction (MVC) and its associated time needed to reach the MVC (TMVC), and the total force generation (TFG) during the sustained task. The hand fatigue was assessed by MVC degeneration (DeltaMVC), the shift in time needed to reach the MVC (DeltaTMVC), and the maximal endurance time (MET) associated with the sustained task. Ten female subjects took part in the experiment voluntarily. The four-gloved conditions included bare hand, wearing one layer (Cotton-1), wearing two layers of cotton gloves (Cotton-2), and covering the handle with two layers of cotton glove and exerting with the bare hand (Covered-2). The results indicates that wearing gloves decreased the grip MVC, and the thicker the gloves, the less the grip MVC, but the wearing style did not change the MVC (Cotton-2 MVC was indifferent from Covered-2 MVC). As to muscular fatigue, on the other hand, wearing gloves did not affect DeltaMVC, MET, TMVC, or DeltaTMVC. Due to the greater bare-hand MVC and indifferent MET, bare-hand TFG was better than those conditions with gloves. Finally, the load specified here did not alter TMVC or DeltaTMVC, but the greater the load, the more strength degeneration (DeltaMVC) was induced.