Police were called to the venue on Friday night after staff reported a number of people in the audience causing a disturbance.
Two people removed by security staff were spoken to by police, and the closing ten minutes of the musical, which stars former Pussycat Dolls singer Melody Thornton, were pulled.
The disruption came two months after similar scenes during a run of Bat Out Of Hell at the Playhouse Theatre in Edinburgh lead to its boss, Colin Marr, warning that anti-social behaviour was becoming “far too regular an occurrence.”
He spoke out after staff members were physically and verbally assaulted by theatre-goers.
The scenes at the Manchester venue underline the growing issues facing theatres as audiences fail to be respectful to people around them, those performing on stage and venue staff.
The disruption of The Bodyguard saw Ms Thornton apologise to fans.
In a video posted to her Instagram story on Friday evening, she said: "I am so grateful to everyone who respect the people on stage who want to give you a beautiful show. I just am very, very sorry that we couldn't finish the show. I fought really hard. It feels awful.”
"The Bodyguard is a great show. It's a wonderful story and love story. And I know people were out to see just a really beautiful show. I thank everyone who was respectful of the performers, and I'm very sorry for those who weren't.”
Greater Manchester Police said: "Officers were called to the Palace Theatre after staff reported a number of people in the audience causing a disturbance.
"Two people removed by security staff were spoken to by police and a decision about any further action will be made once the evidence has been reviewed."
Tash Kenyon, a 27-year-old payroll clerk from the Wirral, told the PA news agency that she and her mother Jan Kenyon, a nurse, had gone to see the show for Jan's 65th birthday.
Tash said: "Before the performance the stewards were walking up and down the aisles with signs saying 'please refrain from singing along' - they were incredibly hard to miss. Two announcements were made as well saying 'please don't sing' and that the audience would have a chance to join in in the finale.
"The show was halted about 20 minutes in as some guests were singing. The guests were removed, and the show continued. The show had about 10 minutes left when the lead started performing I Will Always Love You.
"Someone shouted 'Does this mean we can start singing now?' which set the audience off laughing, and that's when the singing started over the top of the lead's vocals.
"The show stopped a minute later, the lights went on. I couldn't see from my seat but I could hear the commotion from the second tier of seats, and people were looking up shocked.
"I'm pretty sure some women were being forcibly removed.”
A spokesperson for The Palace Theatre said: "We are grateful to our venue teams for dealing with these difficult circumstances in a professional and calm way, and to Greater Manchester Police for their assistance. Future performances will continue as planned.”