Simultaneous chromatographic determination of both ertapenem (ERP) and paracetamol (PCL) was achieved for the first time via a new HPTLC-densitometric method. The developed method relied on a simple planar chromatographic separation by mixture of acetonitrile and water (35:15, v/v) and dual-wavelength detection at λmax of both drugs (294 and 247 nm for ERP and PCL, respectively). The Rf values were 0.74 ± 0.05 and 0.88 ± 0.05 for ERP and PCL, respectively. Under the optimized conditions, the linearity range was 40.0–600.0 and 15.0–200.0 ng band−1 for ERP and PCL, respectively with good correlation coefficients (0.9997 and 0.9998 for ERP and PCL, respectively). The LOD were 13.08 and 3.65 ng band−1 for ERP and PCL, respectively. The method validation parameters were in compliance with the international standards. The developed method was enough sensitive and selective for the determination of ERP in the presence of its open beta-lactam ring degradation product, which makes it a suitable stability-indicating method. Consequently, it was successfully applied for pharmaceutical formulation, spiked and real plasma samples of healthy rabbits for real pharmacokinetic studies of ERP and PCL.