Four novel matrine-based alkaloids (1-4) were isolated from the seeds of Sophora alopecuroides. Compounds 1 and 2 possess unprecedented 6/6/6/4 and 6/5/6/6 ring systems, respectively, while 3 and 4 are a pair of stereoisomeric matrine-acetophenone alkaloids with an unusual skeleton. Their structures were elucidated by means of spectroscopic methods and single-crystal X-ray diffraction. Hypothetical biogenetic pathways for 1-4 are proposed, and their antiviral activities are also discussed.