In this study, continuous-flow membrane microextraction was connected online with a high-performance liquid chromatography-UV detector for the pre-concentration and high clean-up of papaverine and codeine in biological samples. The extraction cell was designed with donor and acceptor chambers separated by a sheet membrane. By adjusting the pH of the donor phase (10 mL, pH 11), the analyte molecules were extracted into the supported liquid membrane (SLM) (15 µL of 1-octanol). The donor solution was circulated through the donor chamber using a peristaltic pump and magnetically agitated by a bar stirrer placed near the membrane, enhancing the diffusion and convection flow of the targeted drugs from the donor solution to the SLM. Subsequently, by adjusting the acceptor solution to an acidic pH of 2 (100 µL), the drugs in ionic form were reversely extracted into the acceptor phase. The procedure exhibited desirable relative standard deviation of less than 3.70%, linear ranges of 7–600 ng mL⁻¹ for codeine and 2.0–600 ng mL⁻¹ for papaverine, and limits of detection of 2.0 ng mL⁻¹ for codeine and 0.6 ng mL⁻¹ for papaverine. The design of the extraction cell significantly improved the performance for determining targeted drugs in complex matrices such as plasma and urine.