Inspired by the natural responsive phenomena, herein the multiple responsive persistent luminescent Zn1.2Ga1.6Ge0.2O4:Ni2+ (ZGGO:Ni) nanoparticles with near‐infrared (NIR) II emission peak ≈1330 nm derived from the Ni2+ doping through controlled synthesis based on hydrothermal method are obtained. The obtained NIR II persistent luminescent ZGGO:Ni can not only respond to temperature but also the specific solvent stimulus. The results demonstrate that the NIR II persistent luminescence intensity decreases in hydroxyl containing solvent such as water (H2O) and ethyl alcohol (C2H6O), while the PL intensity remains in solvent without hydroxyl groups such as n‐hexane (C6H14) and deuterated water (D2O). This NIR II luminescence quenching is attributed to the adsorption of interaction hydroxyl groups in specific solvents with the amino group on the surface of ZGGO:Ni and the subsequent fluorescence resonance energy transfer mechanism. Benefiting from the multiple responsive properties, the obtained NIR II persistent luminescent ZGGO:Ni is utilized for high‐order dynamic optical information encryption, providing increased security level. The multi‐responsive NIR II persistent luminescence strategy outlined in this study is anticipated to offer a straightforward methodology for optimizing the optical characteristics of NIR II persistent luminescent materials. Moreover, it is set to expand the scope of their applications in the realm of dynamic and environment‐interactive information encryption, thereby opening frontiers for their utilization in advanced security measures.