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Gemcitabine (GEM) is commonly chosen for treating pancreatic cancer. However, its use is limited by toxicity. Earlier in vitro studies with GEM in combination with Bromelain (Brom) and Acetylcysteine (Ac) indicated a substantial reduction in IC(50). In this study, immunocytochemistry and Western blot were used to explore the mechanistic effects of Brom and Ac (BromAc(®)) in vitro. Then, we explored the efficacy and safety of BromAc(®) only and with GEM in a pancreatic cancer model in vivo. Immunocytochemistry results revealed a reduction in both MUC1 and MUC4 post-treatment. There was a decrease in VEGF, MMP-9, NF-κβ and cleavage of PARP. There was also a decrease in the cell cycle regulators Cyclin B and D as well as TGF-β and the anti-apoptotic Bcl-2. In vivo, the low and high doses of BromAc(®) alone and with chemotherapy agents were safe. A very significant reduction in pancreatic tumour volume, weight, and ki67 were seen with BromAc(®) therapy and was equal to treatment with GEM alone and better than treatment with 5-FU. In addition, tumour density was significantly reduced by BromAc(®). In conclusion, the anticancer effect of BromAc(®) is probably related to its mucin depletion activity as well as its effect on proteins involved in cell cycle arrest, apoptosis and modulation of the tumour microenvironment. The in vivo results are encouraging and are considered the first evidence of the efficacy of BromAc(®) in pancreatic cancer. These results also provide some mechanistic leads of BromAc(®).