A total of 108 Holstein cows were used to evaluate the effect of drenching propylene glycol (PG) either individually or in combination with glycerol (G) on body condition score (BCS), production, reproductive performance, protection against subclinical ketosis and economic benefit of dairy cows during the transition period. The six groups (n = 18/group) were; Control group, cows received no treatment; PG300, cows were drenched 300 mL PG for 7 days pre-expected day of calving and 21 days post-calving; PG400, cows were drenched 400 mL PG for 7 days pre-and 7 days post-calving; PG500, cows were drenched 500 mL PG for 10 days pre-and 10 days post-calving; GPG150, cows were drenched a mixture of 150 mL G and 150 mL PG for 21 days pre-and 21 days post-calving; GPG250, cows were drenched a mixture of 250 mL G and 250 mL PG for 21 days pre-and 21 days post-calving. BCS at 30 days in milk (DIM) was significantly higher in all treated groups in comparison to the control one and the best values were observed in GPG250, GPG150 and PG500 groups. Lactation length (LL) was significantly (p < 0.001) shorter in GPG250, GPG150 and PG500 groups than control group. There was a significant increment in 305 milk yield (p < 0.001) and average daily milk yield (p < 0.001) in GPG250 and PG500 groups than other groups except for PG300 with the lowest values for control and PG400. Cows in all treatment groups were observed in heat and conceived earlier as well as had shorter open days and calving interval durations (p < 0.001) and low number of services per conception (p = 0.004) compared to control group with better results for PG500 and GPG250 groups. BHB level and percentage of cows suffered from subclinical ketosis at 7 DIM was significantly lower in GPG250, GPG150 and PG500 groups than control group. Cows in treatment groups had a significantly higher glucose level (p = 0.006) compared to control group. Regarding to economics, the control group showed the highest feed costs, insemination costs and total costs per animal. Additionally, control and PG400 groups had the highest cost per kilogram of milk from total and feed costs compared to other cows. PG300, PG500 and GPG250 groups recorded a greater net return and income over feed cost (IOFC). In conclusion, the continuous drenching of propylene glycol either individually or in combination with glycerol regimens for long duration (PG300, PG500, GPG150, GPG250) during the transition period of dairy cows may reduce the incidence of subclinical ketosis and consequently improve milk production, reproduction and economics compared to drenching for short duration (PG400).