An intrinsically luminescent curcumin-modified nanodiamond derivative (ND-Cur) has been synthesized as an effective probe for cell imaging and sensory applications. DLS data allowed the particle size ofND-Curto be estimated (170.6 ± 46.8 nm) and the zeta potential to be determined. The photoluminescence signal ofND-Curwas observed at 536 nm, with diverse intensities at excitation wavelengths of 350 to 450 nm, producing yellow emission with a quantum yield (Φ) of 0.06. Notably, the results of the MTT assay and cell imaging experiments showed the low toxicity and biocompatibility ofND-Cur. Subsequently, investigations of the selectivity towards Mg2+and Mn2+ions were performed by measuring intense fluorescence peak shifts and “Turn-off” responses, respectively. In the presence of Mg2+, the fluorescence peak (536 nm) was shifted and then displayed two diverse peaks at 498 and 476 nm. On the other hand, for Mn2+ions,ND-Currevealed a fluorescence-quenching response at 536 nm. Fluorescence studies indicated that the nanomolar level detection limits (LODs) of Mg2+and Mn2+ions were approximately 423 and 367 nM, respectively. The sensing mechanism, ratiometric changes and binding site were established through PL, FTIR, Raman, SEM, TEM, DLS and zeta potential analyses. Furthermore, the effective determination of Mg2+and Mn2+ions byND-Curhas been validated through cell imaging experiments.