Three series of resins with different functional groups (PS-EA, PS-MP, and PS-BA) based on D101 copolymer were prepared via the atom transfer radical polymerization method. The adsorption capacities of functionalized resins toward matrine (MT) and oxymatrine (OM) depended on the specific surface area, the surface chemistry, and the good polarity match between the target compound and porous material. It is noted that the accumulation of functional groups uploaded on the surface of resins increased the adsorption affinity difference between the MT-functionalized resin system and OM-modified copolymer system. The selectivity of modified resins to MT and OM would attribute to polarity matching. The results could provide a possible strategy for the design of efficient adsorbents applied for the isolation the bioactive compound from complex natural products.