Galanin is a 30 amino acid peptide that stimulates three subtype receptors (GAL1–3R). M89b is a lanthionine-stabilized, C-terminally truncated galanin analog that specifically stimulates GAL2R. We investigated the potential of M89b as a therapeutic for pancreatic ductal adenocarcinoma (PDAC) and assessed its safety. The anti-tumor activity of subcutaneously injected M89b on the growth of patient-derived xenografts of PDAC (PDAC–PDX) in mice was investigated. In addition, the safety of M89b was assessed in vitro using a multi-target panel to measure the off-target binding and modulation of enzyme activities. In a PDAC–PDX with a highGAL2Rexpression, M89b completely inhibited the growth of the tumor (p< 0.001), while in two PDAC–PDXs with lowGAL2Rexpression, low or negligeable inhibition of tumor growth was measured, and in the PDX withoutGAL2Rexpression no influence on the tumor growth was observed. The M89b treatment of theGAL2Rhigh-PDAC–PDX-bearing mice led to a reduction in the expression ofRacGap1(p< 0.05),PCNA(p< 0.01), andMMP13(p< 0.05). In vitro studies involving a multi-target panel of pharmacologically relevant targets revealedexcellent safety of M89b. Our data indicated that GAL2R is a safe and valuable target for treating PDACs with highGAL2Rexpression.