This study focused on developing surrogate indicators for predicting oxidation of phenolic groups in dissolved organic matter (DOM), suppression of halophenols’ formation potential and abatement of estrogenic activity during ozonation of water and wastewater. The evolution of pH-dependent differential absorbance spectra suggests that O3 preferentially reacts with the DOM phenolic moieties and less so with the aromatic carboxylic groups with increasing O3/DOC ratios and changes of UV absorbance and fluorescence. When ozonation used as pretreatment, the formation of halophenols in subsequent chlorination decreased linearly with increasing O3 doses or changes of UV absorbance until it reached 85% suppression of the halophenols’ formation from unaltered DOM. The thresholds of decreases of UVA254, UVA280 and humic-like fluorescence corresponding to 85% suppression of halophenols’ formation were in the range of 25%~30%, 30%~35% and 30%~45%, respectively. Pre-ozonation also showed a moderate suppression of haloacetic acids (HAAs) formation potentials, ≤26.5% for SR_NOM and ≤31.5% for Yangtze River at applied O3 doses. Measurement of changes of estrogenic activity during ozonation of water and wastewater showed that to attain a >90% abatement of estrogenic activity, the corresponding thresholds of decreases of UVA254, UVA280 and humic-like fluorescence were ~30%, ~40%, and ~70%, respectively. Bromate formation was also suppressed to below 10 μg/L before these thresholds. This study suggests that optimal ozonation conditions and a balance between control of disinfection byproducts (halophenols, HAAs and bromate) and elimination of estrogenic activity can be reached based on online data.