Due to their strong hydrophobicity and the aggregation-caused quenching effect, the application of perylene diimide (PDI) dyes in biological and medicinal fields lags far behind that of other dyes. Based on a multifunctional encapsulation strategy, we prepared isopropylphenyl sulfone encapsulated PDI dyes (SFPDIs). The four hydrophilic sulfone groups on the bay position of the PDIs not only effectively inhibit the fluorescence quenching caused by π-aggregation but also endow the SFPDIs with good live-cell permeability. The six lipophilic isopropylphenyl groups encapsulate PDI emitters and confer SFPDIs with excellent lipid droplet-targeting ability. Furthermore, the strong electron-withdrawing sulfone groups give the PDIs excellent anti-oxidation ability.