Carica papaya belongs to Carricaceae family, which has been proven traditionally to treat dengue fever due to its pharmacological properties to increase platelet count. However, during the critical phase of dengue fever, the platelet count will decrease due to the blood vessel rupturing. Therefore, the main objectives of this study were to reduce the bitterness of Carica papaya extract by removing saponin and to study the effect of saponin-reducing extract on the proliferative activity of human lung fibroblast cell (IMR90). For preparative isolation of the saponin compound, peleg model was used to determine the maximum extract concentration, exhaustive time of extraction and total saponin content (TSC) using different weights of dry Amberlite® IRA-67 resin. The remaining saponins in the extract were quantified by mean of RP-HPLC prior to material balance. Then, approximately 1.0 x 104 cells of IMR90 were seeded onto 96-well plate and later treated with various concentrations of extracts for 3 days of incubation. The results showed that, the amount of saponin left in the extract was approximately the same as in the untreated extract (p<0.05). A short adsorption incubation time (2 hrs) was believed to affect the saponin adsorption efficiency. In fact, other bio-active constituents (e.g. polyphenolic compounds) might have been adsorbed as there was a significant depreciation of antioxidant properties on the treated extract (p<0.05). In conclusion, after three consecutively days of extracts-IMR90 cell incubation, the best EC50 values of both untreated and saponin-reducing extracts were observed to be more than 24 hrs of exposure ranging from 104.08 ± 0.90 to 17040.47 ± 2.30 µg/ml. Meanwhile, saponin-reducing extract has been proven not to affect any normal cell growth but in fact it decreased 1.2-fold as compared to the extract containing saponin (control).