Talc has long been a problematic gangue mineral in sulfide ore flotation due to its natural hydrophobicity. The as-investigated anionic depressants which reacted with the Mg sites on the edge plane of talc always exhibited limited effects because the negatively charged talc particle at pH > 5.0 showed electrostatic resistance for the anion adsorption. Thus, an electrically neutral reagent, fenugreek gum, was introduced as a highly efficient talc depressant in comparison with the sodium carboxymethylcellulose and sodium alginate, coupled with the surface detections on the selective depressant mechanism between chalcopyrite and talc. The micro-flotation results showed that fenugreek gum could selectively depress the talc flotation at lower dosage and wider pH range than sodium carboxymethylcellulose and sodium alginate, suggesting a more efficient depressant role. Surface detection implied that fenugreek gum selectively interacted with the basal plane of the talc surface and remarkably decreased its hydrophobicity mainly through physical adsorption originated from the hydrogen-bonding between the OH group and the [SiO4] tetrahedron. Fenugreek gum adsorbed onto talc with much larger capacity than on chalcopyrite, and had little influence on the adsorption density of collector adsorption on chalcopyrite, indicating the highly efficient selectivity of fenugreek gum toward talc depression.