Multi-soil-layering (MSL) system was designed for purifying domestic wastewater and for treating polluted river water. MSL system is typically comprised of layers of soil mixture blocks alternating with permeable layers. The permeable layer has roles of preventing clogging and to increasing the efficiency of infiltration of wastewater through the soil mixture blocks. In this study, the comparative efficiency of five MSL systems as a function of five permeable layer materials (zeolite, zeolitized perlite, perlite, gravel, and charcoal) was investigated. The MSL systems were constructed in 15 × 50 × 100 cm boxes where the soil mixture blocks contained sandy clay soil, kenaf + corncob, and iron scraps at a ratio of 6 : 1 : 1 by weight, respectively, and filled up in alternation with the permeable layer. The results indicated that all the MSL systems at loading rates of 96–346 L m−2 d−1 under nonaerated conditions were able to reduce the levels of COD (342–1,231 mg L−1), BOD5 (201–802 mg L−1), and soluble reactive phosphorus (SRP) (3.5–10.1 mg P L−1) at percentages of 79.0–98.1, 80.0–99.6, and 97.1–100%, respectively. The zeolite and the charcoal-based MSL systems under a 96–346 L m−2 d−1 loading rate effectively reduced the level of TN (41.4–65.5 mg N L−1) at percentages of 79.0–92.1 and 30.7–88.9%, respectively. In terms of prevention of clogging, the charcoal-based MSL system was the most effective, followed by the gravel and zeolite-based MSL. The apparent efficiency of pollutant removal, for zeolitized perlite, perlite, and gravel-based MSL systems was low. With an on-off aeration operation, the efficiency of the MSL systems in the reduction of the levels of COD, BOD5 , and SRP (hereafter reference to as “removal”) was significantly enhanced. Overall, the zeolite-based MSL system seemed to be more effective than the other MSL systems. However, if optimum aeration could be obtained, the removal efficiency of charcoal-based MSL system might be improved. Aeration at a rate of 64,000 L m−3 d−1 for 1 week alternating with 2 weeks of nonaeration enhanced the removal of COD, BOD5 , and SRP but not that of TN.