Synthesis of Schiff bases B1–B15 followed several steps. The 4-amino-5-(4-methyl-2-phenylthiazol-5-yl)-4H-1,2,4-triazole-3 thiol 4 was obtained by treating potassium 2-(4-methyl-2-phenylthiazole-5-carbonyl)hydrazine-carbodithioate 3, previously obtained, with hydrazine hydrate. The final derivatives were synthesized in good yields by the condensation of compound 4 with various aromatic or heteroaromatic aldehydes.Schiff bases were investigated for their anti-Candida potential. The in vitro methods used were the disk diffusion disk, the determination of MIC and MFC, respectively. The activity of the new derivatives was reported to reference drugs, already used in therapy. Some of the Schiff bases showed MICs inferior to those of the references used. Compound B10 showed to be the most promising anti-Candida candidate, inhibiting the growth of all three Candida strains used and being more potent than fluconazole. The obtained results suggest that the new series bearing thiazole and triazole scaffolds may be considered for further investigation and optimization, in designing anti-Candida drugs.A docking study of the thiazolyl-triazole Schiff bases was performed on compounds B1–15 and presented a rationale for the activity of these compounds. Performed on CYP51 enzyme, this study showed that the thiazolyl-triazole Schiff bases interact with the amino acids in the access channel to the active site of the lanosterol 14?-demethylase with higher binding affinity energy than fluconazole. Moreover, the compounds do not interact with the heme.Furthermore, a virtual study was performed to predict the ADME and the toxicity of the derivatives. The studied compounds showed an acceptable gastro-intestinal absorption and a low to moderate water solubility. We could predict the absence of toxicity at CNS level, due to the fact that the compounds do not pass the blood–brain barrier. All of the newly synthesized compounds were predicted as noninhibitors of CYP2D6, noninducers of phospholipidosis, and they are not a substrate for P-glycoprotein. All these observations will be helpful in designing newer anti-Candida agents with good pharmacokinetic properties and without severe side effects.