Display omitted •The nonlinear optical properties of LDS 821 in different solvents were investigated.•The nonlinear optical properties of LDS 821 dye were predicted theoretically.•Linear and nonlinear optical properties of LDS 821 dye in DNA was investigated.•The influence of dihedral angle on nonlinear optical properties of LDS 821 dye on DNA was studied. Linear and nonlinear optical properties of near-infrared laser grade dye LDS 821 in different solvents and Salmon Deoxyribonucleic acid (DNA) were studied using spectroscopic and Z-scan techniques. UV–Vis absorption spectrum of the dye shows a bathochromic shift with a decrease in the solvent polarity parameter, and in DNA, the dye exhibits a hypochromic shift. The fluorescence spectrum of the dye does not show any notable correlation with the solvent polarity parameter, but in DNA, the fluorescence intensity of the dye decreases with the incremental addition of DNA. Molecular docking studies reveal that the dye intercalates on the major grooves of DNA. Nonlinear optical properties of the dye in different solvents and phosphate buffer solution with varying DNA concentrations were studied using the Z-scan technique using a Q-switched Nd: YAG laser operating at fundamental and second harmonics. A closed and open aperture Z-scan of dye in different solvents was carried out to estimate the nonlinear refractive index, excited-state absorption cross-section, and two-photon absorption coefficient (TPA). The variation in nonlinear optical properties of the dye in different solvents was due to solvent-induced structural modifications. Theoretical investigation on nonlinear optical properties of the dye in different solvents was carried out using density function theory. The theoretical first and second-order hyperpolarizability was calculated using B3LYP functional. The predicated nonlinear optical parameters of the dye in different solvents does not show any direct correlation with solvent polarity. Nonlinear absorption of the dye in phosphate buffer solution (PBS) and DNA were estimated. The nonlinear absorption of the dye in PBS decreases with the addition of DNA. Molecular docking studies were carried out to determine the structural changes induced in dye due to the intercalation with DNA.