Water contamination with antibiotics promotes environmental antibiotic resistance. Tetracycline(TC), commonly used in agriculture, pollutes water and enables bacteria to develop resistance genes. Mg-Al-layered double hydroxides/Activated carbon (Mg-Al-LDH/AC) nanocomposite effectively removes tetracycline from water in this study. The synthesized adsorbent was characterized using Brunauer–Emmett–Teller (BET), Fourier-transform Infrared Spectroscopy (FT-IR), Field Emission Scanning Electron Microscopy (FESEM), X-Ray Diffraction (XRD), and Energy-dispersive X-ray spectroscopy (EDS) tests, and exhibited a large surface area of 105.46 m2/g, a total pore volume of 0.4571 cm3/g, and an average pore diameter of 27.99 nm. The optimal conditions for eliminating TC using the Mg-Al-LDH/AC nanocomposite were determined via the central composite design response surface methodology (CCD-RSM) approach. The responses were evaluated using a second-order polynomial multiple regression model, which was found to be a satisfactory fit to the data based on the analysis of variance (R2 = 0.9690, R2Adj = 0.9478, and R2Pred = 0.9042). The ideal conditions were identified as pH = 5.1, 0.11 g of adsorbent, a TC concentration of 50 mg/L, and a contact time of 90 min. The adsorption isotherms showed that TC elimination follows the Langmuir model with a maximum adsorption capacity of 106.4 mg/g and a high R2 value of 0.9986. The kinetics of the TC adsorption process was found to fit the pseudo-second-order model with a correlation value of 0.9997. The values of ΔG, ΔH, and ΔS for TC were determined to be 1.90 kJ/mol (at 333.15 K), −41.97 kJ/mol, and −0.131 kJ/(mol·K), respectively. Additionally, the study showed that ionic strength did not affect the effectiveness of TC removal, and the adsorbent was effective in removing TC antibiotics in a range of ionic strengths. Finally, the study found that adding 20% by weight of AC to LDH resulted in the best TC removal efficiency.