Background: Pain is a common problem encountered in daily life among humans and animal and it is commonly managed conventionally using modern medicines and traditionally by use of medicinal plants. Phytolacca dodecandra is a common herb in Uganda, used traditionally to alleviate pain and inflammatory conditions. However, its activity in alleviating pain and inflammatory diseases has not been fully scientifically evaluated. Aim of Study: To evaluate the analgesic and anti-inflammatory activity of total crude leaf extracts of P. dodecandra in Wistar albino rats. Materials and Methods: It was a laboratory-based experimental study. Acetic acid-induced writhing test was used to determine the analgesic activity and the histamine-induced paw edema formation for anti-inflammatory activity of the extract. Twenty eight animals were divided into 7 groups each with 4 rats and two (2) sets of data were obtained from each animal per group as per guidance of the refinement rule of 3Rs. For analgesic activity, Group I was dosed with 1.0ml of normal saline (negative control), group II, III, IV, V, VI were dosed with 1000.0, 600.0, 150.0, 40.0 and 5.0 mg/kg bwt of extract respectively. Group VII was dosed 10.0 mg/kg bwt diclofenac sodium (Na) drug (positive control). For anti-inflammatory activity, Group I was dosed with 1.0ml of normal saline (negative control), Group II, III, IV, V, VI were dosed with 1000.0, 600.0, 300.0, 40.0 and 5.0 mg/kg bwt of extract respectively. Group VII was dosed 10.0 mg/kg bwt diclofenac Na. The percentage mean paw volume inhibition and percentage writhing protection were determined. Results: The mean percentage paw volume inhibitions were 29.1%, 74.2% and 32.