A chemical investigation of the stem of Waltheria indica (Malvaceae) yielded twelve 4-quinolone alkaloids, which were primarily waltheriones. These were waltherione A (1), waltherione B (2), waltherione C (3), waltherione G (4), waltherione H (5), waltherione J (6), waltherione L (7), waltherione P (8), chamaedrone (9), 8-deoxy-antidesmone (10), antidesmone (11), and the previously unreported alkaloid N-methoxy-waltherione A (12). These alkaloids belong to an unusual class of 4-quinolones and therefore, have chemosystematic significance for distinguishing the Waltheria and Melochia genera from the rest of the Malvaceae family. The ability of the alkaloid isolates to reverse the phenotypic expression of fluconazole-resistance was tested by using a mutant strain of Saccharomyces cerevisiae that expressed a Candida albicans transporter. Of the isolates tested, waltherione G afforded a positive result. Leishmanicidal activity and bactericidal tests were also performed using the isolated alkaloids, which showed promising results.