Novel tocopherol derivatives and tocopheryl quinone derivatives useful in the decrease of lysosomal substrate accumulation, the restoration of normal lysosomal size, and the treatment of lysosomal storage disorders (LSDs) are provided. The inventors have discovered that tocopherol and tocopheryl quinone derivatives with side chain modifications (such as terminal tri-halogenated methyl groups) exhibit improved pharmacokinetics, modulation of mitochondrial potential and restoration of some LSDs phenotypes. These molecules by themselves or in combination with Cyclodextrins (CDs) increase intracellular Ca2+ and enhance exocytosis. Also, the treatment with these compounds reduced the pathological changes in the ultrastructure of LSD cells as observed using electron microscopy analysis. The inventors also found that there is a synergy between CDs and the new tocopherol analogues when tested on the NPC cells and cells from six other lysosomal storage diseases including Wolman, Niemann Pick Type A, Farber, TaySachs, MSIIIB and CLN2 (Batten) diseases. These new tocopherol analogues are as good or better than natural occurring tocopherols and tocotrienols in reducing cholesterol accumulation in several LSDs.