Barbatic acid, a compound isolated from lichen, has demonstrated a variety of biological activities. In this study, a series of esters based on barbatic acid (6a–q′) were designed, synthesized, and evaluated for their diuretic and litholytic activity at a concentration of 100 μmol/L in vitro. All target compounds were characterized using1H NMR,13C NMR, and HRMS, and the spatial structure of compound6wwas confirmed using X-ray crystallography. The biological results showed that some derivatives, including6c,6b′, and6f′, exhibited potent diuretic activity, and6jand6mdisplayed promising litholytic activity. Molecular docking studies further suggested that6b′had an optimal binding affinity to WNK1 kinases related to diuresis, while6jcould bind to the bicarbonate transporter CaSR through a variety of forces. These findings indicate that some barbatic acid derivatives could be further developed into novel diuretic agents.