Nowadays, the use of a suitable membrane with high permeation and removal properties in separation processes has become a competitive necessity in water purification and desalination. Nanostructured membranes have encouraged many researchers and industrialists to use them. Hence, the use of mixed matrix membrane (MMM) has been considered due to its high removal efficiency. Herein, a nanocomposite (NC) of carboxylated multiwalled carbon nanotubes (MWCNTs-COOH) and MIL-53(Al) was introduced as an innovative modifier for polyethersulfone (PES)-based nanofiltration (NF) membrane. Five membranes with different MIL-53(Al)/MWCNTs loadings (1, 3, 5, 7, and 9 wt%) were prepared and characterized by SEM, XRD, FTIR, and AFM techniques. The effect of MIL 53(Al)/MWCNTs on the physicochemical and structural properties of the MMMs was investigated by considering water flux, hydrophilicity, antifouling, and rejection of dyes and bioactive materials (e.g., amoxicillin and bovine serum albumin). The membrane porosity enhanced to 74.43 % after incorporation of 5% MIL-53(Al)/MWCNTs to the PES polymer matrix, compared with the porosity of the bare membrane (67.50 %). Furthermore, the membrane water contact angle decreased to 32.46 degrees by addition of MIL-53(Al)/MWCNTs to the matrix (cf. 62.10 degrees for the bare membrane). The introduction of MIL-53(Al)/MWCNTs significantly increased the membrane water flux from 14.8 to 246.2 L/m2.h. The modified membrane containing 5% of MIL-53(Al)/ MWCNTs showed excellent performance with the removal of 98%, 77 %, 93.07%, and 97% for methylene blue (MB), methyl orange (MO), amoxicillin (AMOX), and bovine serum albumin (BSA), respectively with enhanced flux recovery ratio (FRR) of 64.3%. Therefore, PES/MIL-53(Al)/MWCNTs MMMs showed high potential for water treatment.