Chiral covalent triazine frameworks (CCTFs), as emerging chiral organic porous polymer materials, have many special properties, such as being rich in nitrogen, having a large surface area, adjustable porosity, and high chemical stability, etc., making them an attractive separation medium for HPLC enantioseparation. Herein, a novel chiral core–shell composite CC-DMP CCTF@SiO₂ with uniform spherical particles was synthesized by an in situ growth method. The prepared chiral core–shell microspheres CC-DMP CCTF@SiO₂ were adopted to resolve chiral compounds by HPLC. The results showed that the CC-DMP CCTF@SiO₂ packed column exhibited good separation performance and high column efficiency (e.g., 17 580 plates m⁻¹ for 4-methylbenzhydrol) under a low column back pressure (5–9 bar) for HPLC separation of different chiral compounds such as alcohols, amines, ketones, and so on. Among them, the resolution values of naringenin and 1-phenyl-1,2-ethanediol were 4.24 and 4.09, respectively. Comparing the chiral recognition capacity of the CC-DMP CCTF@SiO₂ packed column with those of commercial Chiralpak AD-H and the previously reported CCOFs@SiO₂ (CTpBD@SiO₂, β-CD-COF@SiO₂) columns, the CC-DMP CCTF@SiO₂ packed column can be complementary to the Chiralpak AD-H and CCOFs@SiO₂ columns. The effects of the injection amount and column temperature on the separation process were also studied. The CC-DMP CCTF@SiO₂ packed column exhibited good reproducibility and stability after multiple injections. The relative standard deviations (RSD_S) of the retention time and peak area for repeated separation of 4-methylbenzhydrol (n = 5) were 0.45% and 0.87%, respectively. This work suggests that the chiral CC-DMP CCTF@SiO₂ core–shell microsphere composite has a promising application as a novel CSP material in HPLC.