Condensation of α-pinene derived p-menta-1,8-diene-5,6-diol (diol) with decanal was studied for the first time over modified halloysite nanotubes (HNT). The yield of the desired hexahydro-2H-chromene-4,8-diol with analgesic activity was 76–80 % practically not depending on the catalyst type, while selectivity to 4S-isomer decreased, and to 4R-isomer increased with increasing acidity. The highest selectivity to 4S-diastereomer (48.1 %) on halloysite is a result of weak acidity of this catalyst. DFT optimization of the key intermediate structure shows that the nucleophile attack proceeds at the equatorial position with the 4S-diastereomer formation, which was preferred on halloysite. On strong Brønsted (Amberlyst-15) and Lewis (scandium triflate) acids the target product yield did not exceed 37 % because of dehydration. Halloysite nanocatalysts displayed a stable performance. In the case of diol reaction with a set of carbonyl compounds, the yields of hexahydro-2H-chromene-4,8-diols (up to 88.0%) and the ratio of its 4S/4R isomers (up to 21.0) were significantly higher than on other catalysts.