I report surface modification of up-converting, Er³⁺ and Yb³⁺ co-doped β-NaYF₄ nanoparticles with four types of chiral molecules with proven molecular chiral recognition abilities: L-cysteine, L-penicillamine, L-arginine and L-glutathione. The presence of chiral ligands near to the nanoparticle surfaces was confirmed based on Fourier transform infrared spectroscopy and circular dichroism measurements. The performed post synthetic treatment of nanoparticle surfaces led to stable water solutions, and the best results regarding the long term colloidal stability were found for nanoparticles functionalized with L-penicillamine. The selected chiral molecules were also found to strongly influence the spectroscopic properties of NaYF₄:Er³⁺,Yb³⁺ nanoparticles, including the change in power dependence slopes for blue, green and red emission and luminescence lifetimes. Nevertheless, the high up-conversion emission intensity was preserved after functionalization. The obtained results open up new perspectives for possible applications of up-converting β-NaYF₄ NPs as optical markers in chiral recognition and sensing of chiral drugs.