Orochimaru commonly uses cursed seals on his most powerful followers. To apply a cursed seal, Orochimaru needs to actually bite his intended target. Because he has sharp fangs and an extendable neck, this is a relatively simple task. The seal then appears somewhere on the target's body, and they subsequently lose consciousness. Sometime later, should they survive, they will awaken with the first level of the seal active and be enraged due to the seal's influence. The seals work by forcibly drawing chakra from the user's body, as well as increased physical performance.

The seal has two different levels, and the types of transformations differ from seal to seal. When inactive, the seal is simply a black tattoo on the user's body. Orochimaru has a wide array of cursed seals, so the appearance of the seal will usually vary from user to user. Each seal always has three identical marks arranged in a circular pattern. When first activated, the marks on the seal glow and replicate, spreading over the user's body. This is known as the first level of the seal. The degree to which this occurs is dependent on the user, and the degree to which it spreads is proportionate to the overall effect it has. Normally, the wearer of the seal will also experience slight pains during the activation of this level. The second and final level of the seal causes the black marks to completely envelop the user. This is followed by an unnatural alteration of the user's body, with the only common features being yellow eyes with a black sclera. When in this level, the seal eats away at the user's personality, driving them to madness if used too long. It also takes quite a toll on their body, since they are being mutated by the seal. Aside from the first and second levels of the seal, skilled users of the seal are able to perform partial transformations in which the aforementioned mutation caused to the users body in the level two state can be used without completely altering the entire body. The power of the cursed seal can even synchronize with the user's regular body with extended use (as stated by Sasuke during his second fight with Naruto), increasing the power of his/her natural state.