Drusilla has the standard powers and vulnerabilities of a vampire. She is immortal, regenerates damage, drains human blood to survive, and is stronger than most humans. Drusilla's technique in combat, although awkward-looking, has allowed her to hold her own in a fight against Angel (in "Reunion") and Spike (in "Becoming, Part Two"), along with holding her own against Kendra the Vampire Slayer (in "Becoming, Part One") before using the hypnosis technique. Like all vampires (unless they possess rare protective items, such as the Gem of Amarra), she is vulnerable to holy items and sunlight, can be killed by decapitation or a stake to the heart, and cannot enter the home of a living human without being invited by someone who lives there first.

Drusilla is also a seer with minor psychic abilities. She receives vivid visions that contain possible glimpses of the future, and can also see into people's minds and project false imagery into them (e.g. in Becoming, Part Two, when she convinces Giles that she is really Jenny Calendar). Drusilla had these powers since before being made a vampire; their source or cause is unknown. She is also capable of hypnotizing people, mesmerizing her prey and rendering them helpless, which she achieves by catching their gazes, pointing her fingers towards her victim's eyes and whispering to them ("Be in me"). Drusilla uses this technique to murder Kendra in the episode "Becoming, Part One," and earlier in Season Two taunts and threatens Spike's academic minion with her talents. The Master uses a similar skill to paralyze Buffy in "Prophecy Girl." Drusilla also induces Giles, weakened by Angelus' torture, to perceive her as his murdered love Jenny Calendar ("See with your heart"), and obtains the essential information to complete the ritual of the wakening of Acathla.