Two new alkaloids named piperlactam S and piperine S have been isolated from the stem and leaves of Piper puberullum, in addition to puberullumine and three known pyridone alkaloids. The structures of these compounds were determined on the basis of spectral analyses. The known compounds were identified as piplartine dimer, piplartine and 8,9-dihydropiplartine and obtained for the first time from this species.