The conventional delivery systems are ineffective in therapeutics because of poor adsorption at target site. Conversely, 2D sheet based materials are the advanced drug delivery systems that provide decent adsorption and good attraction with drug molecules and can be used as a carrier of effective drug delivery. In this case, we show two-dimensional (2D) porous covalent triazine framework (CTF-2) as a Drug Delivery System to cyclophosphamide and purinethol (Anticancer Drugs). The CTF-2 cavity interacts with both the cyclophosphamide (CP) and purinethol (PU) drugs. The interactions of the drug with the surface are stabilized by the calculated binding energies favoring the adsorption of the drug molecules on the CTF-2 surface. The geometric and electronic properties of the both drugs inside the cavity of CTF-2 are used to confirm the interactions among the drugs and their potential delivery. The adsorption energies of CP@CTF-2 and PU@CTF-2 complexes are − 1.04 eV and − 0.82 eV. However, the BSSE corrected energy values of CP@CTF-2 and PU@CTF-2 complexes are − 1.02 eV and − 0.80 eV. The outcome of the NCI and the QTAIM analysis has given the explanation that the van der Waals interactions are an important factor in the stabilization of the CP@CTF-2 and PU@CTF-2 complexes. The transfer of charge between the drug and the carriers is explained through the NBO and EDD analysis. FMO analysis showed that HOMO-LUMO gap of the CP@CTF-2 complex (6.92 eV) and the PU@CTF-2 complex (6.62 eV) were both smaller than that of the bare CTF-2 surface (7.10 eV). Dipole moment (µ) and pH can help one to understand the interaction of the drug molecules with the carrier and the surrounding environment especially in drug delivery. These studies shows how these drugs can be loaded and off-loaded using the CTF-2 carrier. This study demonstrates the potential of CTF-2, which is an innovative and promising drug delivery carrier in the treatment of various diseases.