The tennis ace said she had even been dishing out pregnancy advice to the Duchess of Sussex as she prepared to become a mum.
The sports icon told PEOPLE: "I’m like, ‘How are you?’ and she’s like, ‘No, how are you?’ and I’m like, ‘You’re so sweet, but I’m really asking – how are YOU?’"
She added: "I’m like, ‘Meghan, stop being so nice…you’re the pregnant one, aren’t you supposed to have hormones, why are you so sweet?’ But that’s always been her."
Serena's advice came as the former American actress is said to have clashed with Kate Middleton, including in the lead up to her May wedding.
The Duchess of Sussex, 37, reportedly made the Duchess of Cambridge, 36, cry after Princess Charlotte's flower girl dress fitting, with the pair also having been locked in a "ghastly row" over the treatment of staff.
A furious Duchess of Cambridge recently slapped down Meghan after she spoke rudely to a member of Kate's staff telling her doing so was "unacceptable".
Meghan and husband Prince Harry are moving from their London pad, where they live next door to Prince William and Kate, to Frogmore Cottage ahead of the arrival of their baby in the spring of 2019.
It has even been suggested that the 37-year-old is researching "hypnobirthing" ahead of her due date.
But pal Serena said her advice to first-time mums was "it will come".
She said: "I don’t know what’s going to happen, I didn’t know how I’m going to have a baby, and it all came
"It’s so crazy, I totally changed, and it literally is like a switch. And so, I say that, ‘It will come.’"
Serena Williams was one of the many star-studded guests to attend Meghan's wedding to Prince Harry at St George's cathedral in May.
And despite Meghan's new role as a royal, the former Suits star has continued to support her sports icon friend – heading to watch the star at Wimbledon this year.
But after the outing, body language experts said the difference between Kate and Meghan had been pronounced.
Body language expert Judi James told Fabulous Online: “The more reserved Kate has been slowly, carefully and gradually growing into her role in the royal family to the point where she is now showing all the signs of becoming its matriarch.
“Meanwhile, Meghan's glamorous Hollywood lifestyle allowed her to integrate quickly and with much higher levels of confidence. She is a campaigner, feminist and a performer."
A royal insider has since claimed the reported "tit for tat" could bring the monarchy to its knees.
It comes amid claims the Duchess of Sussex is unpopular with palace staff, with some branding her "dictatorial" and say she emails them instructions as early as 5am.
Household staff were reportedly left astounded when she demanded air fresheners to fix the "musty" smell at St George's Chapel before her wedding, but Buckingham Palace officials said no.
And recently her assistant of just six months, Melissa Toubati, who played a "pivotal role in the success of the Royal Wedding", quit the job after "putting up with a lot".
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