We have analyzed peptides, proteins, and protein-drug complexes through surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) using HgTe nanostructures as matrixes. We investigated the effects of several parameters, including the concentration of the HgTe nanostructures, the pH of the buffer, and the concentration of salt, on the performance of this system. When HgTe nanostructures are used as matrixes, [M + H](+) ions were the dominant signals. Relative to other commonly used nanomaterials, HgTe nanostructures provided lower background signals from metal clusters, fewer fragment ions, less interference from alkali-adducted analyte ions, and a higher mass range (up to 150,000 Da). The present approach provides limits of detection for angiotensin I and bovine serum albumin of 200 pM and 14 nM, respectively, with great reproducibility (RSD: <25%). We validated the applicability of this method through the detections of (i) the recombinant proteins that were transformed in E. coli, (ii) the specific complex between bovine serum albumin and l-tryptophan, and (iii) a carbonic anhydrase-acetazolamide complex. Our results suggest that this novel and simple SALDI-MS approach using HgTe nanostructures as matrixes might open several new ways for proteomics and the analysis of drug-protein complexes.