The issue of fatigue is quite topical for the modern humanity. In order to work harder and earn as much money as possible, a person takes various stimulants, which have a number of side effects. This problem is especially serioous in Asian countries. To prevent such complications, scientists are trying to invent actoprotectors that would have minimal side effects. 1,2,4-triazole derivatives have proven themselves well as new substances with different spectrum of pharmacological activity. The aim of this work is the investigation of actoprotective activity of new 3-(thiophen-2-ylmethyl)-1H-1,2,4-triazole-5-thiol derivatives. Materials and methods. To study the actoprotective activity of new 3-(thiophen-2-ylmethyl)-1H-1,2,4-triazole-5-thiol derivatives, a group of 7 white nonlinear rats weighing 200–260 g was used. Pharmacological activity was studied with the method of forced swimming. The study compounds, as well as the reference standard – Riboxin® (manufactured by Kyiv Vitamin Plant) was administered orally 20 minutes prior to the immersion of animals at a dose of 100 mg/kg. For comparison, we also used a control group of animals that received saline 20 minutes prior to the immersion. Gravimetric measurements were performed on laboratory electronic analytical scales model ESJ-200-4(US). Statistical results were calculated using Kolmogorov–Smirnov test and Shapiro–Wilk test. Results. As a result, the actoprotective activity of 22 new compounds was investigated. Compounds Ia, IIb, IIh have been found to have an actoprotective effect. Compound Ia surpasses the comparison drug. The most active substance among the first synthesized salts is the potassium 2-((3-(thiophen-2-ylmethyl)-1H-1,2,4-triazol-5-yl)thio)acetate, which surpasses the comparison drug riboxin by 6.32 %. Conclusions. Some conclusions are drawn regarding "structure - actoprotective effect" dependence: replacement of potassium cation by sodium cation leads to a decrease in biological activity; introduction of 4-chlorobenzylidene or 2,3-dimethoxybenzylidene substituent into the molecule of 2-((3-(thiophen-2-ylmethyl)-1H-1,2,4-triazol-5-yl)thio)acetohydrazide does not affect the actoprotective effect; introduction of benzylidene substituent, 3-nitrobenzylidene, 4-dimethylaminobenzylidene, 2,4-dimethylbenzylidene into the molecule of 2-((3-(thiophen-2-ylmethyl)-1H-1,2,4-triazol-5-yl)thio)acetohydrazide negatively affects the fatigue in rats.